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86 publications mentioning mmu-mir-378a

Open access articles that are associated with the species Mus musculus and mention the gene name mir-378a. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

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[+] score: 434
However, exogenous expression of miR-378a-3p reduced the expression of Gli3 and Gli2 in LX2 cells, suggesting that downregulation of Gli3 by miR-378a-3p did have an effect on the expression of Gli2, which is in agreement with previous reports that Glis mutually influence each other's expression 39 40. [score:12]
In conclusion, our study demonstrates that miR-378a-3p suppresses the activation of HSCs by targeting gli3, and that Hh-responsive Smo represses the transcriptional expression of miR-378a-3p through p65, promoting the activation of Hh and profibrotic genes by increasing the expression of the Hh target genes, Gli2 and Gli3, during liver fibrosis. [score:11]
In LX2 cells transfected with miR-378a-3p mimic, similar results were observed; the level of Gli3 and Gli2 was reduced and the expression of profibrotic markers, vimentin, plasminogen activator inhibitor-I (pai-I) and connective tissue growth factor (ctgf) was also downregulated 25, but gfap was upregulated (Supplementary Fig. 7). [score:11]
Both of pri-miR-378a and miR-378a-3p were downregulated in radiation -treated liver, whereas they were upregulated in irradiated liver treated with Smo inhibitor. [score:9]
These results suggest that upregulation of Gli3 expression is related to significant reduction of miR-378a-3p targeting gli3 in chronically damaged liver. [score:8]
Thus, genome-wide screening of miRNA expression using the more advanced version provided the updated miRNA expression profiles in liver fibrosis and revealed that expression of miR-378 family members including miR-378a-3p, miR-378b and miR-378d were the most significantly reduced among the differentially expressed miRNAs in CCl [4] -induced liver fibrosis, compared with control. [score:8]
As miR-378a-3p is greatly downregulated in LX2 cells, the inhibitory effect of p65 in miR-378a-3p expression seems to be poor. [score:8]
Those findings suggest that the expression level of miR-378 also influences the expression of Hh signalling in hepatocytes and LSECs, including HSCs, by regulating Gli3 expression. [score:8]
Therefore, these results indicate that Smo promotes nuclear localization of p65, which then binds to the miR-378a gene and inhibits transcription of miR-378a to pri-miR-378a, suggesting that reduction of miR-378a-3p expression by Smo-activated p65 contributes to increased expression of Gli3 in aHSCs. [score:7]
Treatment with tumour necrosis factor-α (TNF-α), an activator of NF-κB signalling, induced upregulation of p65 but downregulation of pri-miR-378a and miR-378a-3p in HepG2 cells (Fig. 6b). [score:7]
It was also reported that the miR-378a-3p was abundant in cardiomyocytes, but was downregulated and induced the upregulation of TGF-β1 during cardiac fibrosis 29. [score:7]
We found that expression of miR-378a-3p decreased but expression of gli3 mRNA increased in tumour compared with non-tumour tissues from each HCC sample, demonstrating the correlation of expressional regulation between miR-378a-3p and gli3. [score:7]
Although miR-378a-3p was shown to be unbound to the gli2 mRNA (Fig. 3c), the miR-378a-3p mimic also reduced the expression of Gli2 at 24 h, implying that miR-378a-3p was indirectly regulating Gli2 expression through the interaction between Gli3 and Gli2 (Fig. 4a–c). [score:7]
Seven miRNAs (mmu-miR-574-5p, mmu-miR-466i-5p, mmu-miR-342-3p, mmu-let7i-5p, mmu-miR-34a-5p, mmu-miR-188-5p and mmu-miR-5119) were upregulated and the other five (mmu-miR-378a-3p, mmu-miR-202-3p, mmu-miR-378b, mmu-miR-378d and mmu-miR-212-3p) were downregulated in the CCl [4] group compared with the control (Fig. 1a,b). [score:6]
Interestingly, inhibition of Smo induced the upregulation of pri-miR-378a and miR-378a-3p at 12 and 24 h post GDC-0449 treatment (Fig. 5b,c). [score:6]
Therefore, these results demonstrate that miR-378a-3p suppresses the activation of HSCs by directly targeting gli3. [score:6]
As most upregulation of miR-378a-3p was observed in CCl [4] -treated liver at 3 weeks post NPs/M treatment, we assessed the expression of Gli3 and genes related with HSC activation at this time point. [score:6]
Similar to these findings, pri-miR-378a in NF-κB inhibitor -treated LX2 or HepG2 cells was more upregulated compared with miR-378a-3p at 24 h. These data suggest that p65 functions as a repressor of transcriptional regulation of miR-378a-3p. [score:6]
In line with these results, our data showed that members of miR-378 were upregulated in the qHSCs and its' expression in these cells was similar with it in hepatocytes. [score:6]
MiR-378a-5p was upregulated and influenced SULT2A1 expression in primary sclerosing cholangitis (PSC) 17. [score:5]
However, the expression level of pri-miR-378a and miR-378a-3p was higher in both LX2 and HepG2 cells treated with the NF-κB inhibitor, Bay 11-7085, than in vehicle -treated cells (Fig. 6c). [score:5]
Hence, we checked the expression of miR-378a-3p in the liver of Smo -suppressed mice with radiation. [score:5]
Compared with CCl [4] -treated mice with or without NPs/NC, expression of miR-378a-3p was significantly upregulated in CCl [4] -treated mice with NPs/M-injection and gradually increased after NPs/M treatment, suggesting that NPs/M migrated into and stably released RNA oligonucleotides in the liver during this period (Kruskal–Wallis test and unpaired two-sample Student's t-test, P<0.05) (Fig. 7a). [score:5]
Recent studies report that miR-378a suppresses the growth of hepatitis B virus-related HCC by targeting the insulin-like growth factor 1 receptor 53. [score:5]
Although Gli2, another Hh target gene, was predicted to be a potential target of miR-378a-3p, no binding interaction between gli2 and miR-378a-3p was observed. [score:5]
In addition, in primary aHSCs transfected with a miR-378a-3p mimic, expression of the profibrotic genes encoding for Vimentin, α-SMA, Col1α1 and Mmp-9 decreased, whereas expression of glial fibrillary acidic protein (gfap), an inactivation marker of HSCs 16 24, increased (Fig. 4d). [score:5]
As miR-378a-3p targets Gli3 and the Glis are activated by stimulated Hh receptors, it is possible that Smo influences expression of miR-378a-3p. [score:5]
This elevated expression of pri-miR-378a by Smo suppression suggested that Smo might influence the level of pri-miR-378a transcription. [score:5]
Reduced miR-378a-3p directly and indirectly increases Gli3 and Gli2, respectively, which accelerate the Hh signalling pathway and the expression of fibrotic genes, eventually promoting liver fibrosis (Supplementary Fig. 13). [score:5]
Taken together, our results indicate that miR-378a-3p could be a potential target for diagnosing and treating liver disease with activated Hh signalling. [score:5]
Activation of NF-κB by Smo suppressed transcriptional expression of miR-378a-3p and the reduced miR-378a-3p caused an increase in Gli3 and Gli2, which in turn accelerated or promoted the Hh signalling and fibrotic response. [score:5]
Interestingly, the amount of miR-378a-3p expression was inversely correlated with the hepatic level of Gli3 expression in those mice (Spearman's rank correlation analysis, r=−0.733, P=0.007, n=12) (Supplementary Fig. 5d). [score:5]
Expression of miR-378 was also reduced in Hh-responsive LSECs, compared with both of the qHSCs and the hepatocytes that express lower Hh signalling (Fig. 2). [score:4]
Among these miRNAs that were dysregulated in liver fibrosis, several miR-378 family members, including miR-378a-3p (0.395-fold), miR-378b (0.390-fold) and miR-378d (0.372-fold), had the lowest expression in the livers of CCl [4] -treated mice. [score:4]
These results supported the regulatory effect of Smo in the expression of miR-378a-3p through p65 activation. [score:4]
Wunsch et al. 17 demonstrated that PSC is characterized by disease-specific impairment of SULT2A1 expression, which is regulated by miR-378a-5p. [score:4]
Smo regulates expression of miR-378. [score:4]
These results demonstrated that miR-378a-3p delivered by NPs led to downregulation of Gli3, which promoted inactivation of HSCs in the livers of CCl [4] -treated mice. [score:4]
How to cite this article: Hyun, J. et al. MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression. [score:4]
Expression of miR-378a is regulated by Smo -dependent activation of p65. [score:4]
After 6 h, the medium was changed with fresh medium containing 2% FBS and 1% P/S, and then these transfected cells were incubated at 37 °C and 5% CO [2] atmosphere for 24 or 48 h. To inhibit Smo, fully activated LX2 cells were treated with Vismodegib (1 μM of GDC-0449; Selleck Chemicals), Smo antagonist or vehicle (DMSO) for 24 and 48 h. To assess the regulation of pri-miR-378a expression by NF-κB, HepG2 cells were treated with TNF-α (100 ng ml [−1]), activator of NF-κB signalling or vehicle (PBS), and LX2 and HepG2 cells were treated with Bay 11-7085 (2 μM), repressor of NF-κB or vehicle (DMSO) for 24 h. To evaluate the relationship of Smo with NF-κB, LX2 and HepG2 cells were treated with GDC-0449 (1 μM) for 18 h, followed by addition of TNF-α (100 ng ml [−1]). [score:4]
To assess whether this reduction in levels of the miR-378 family also occurs in other types of liver injury mo dels, we examined the expression of miR-378 family members in livers from mice fed with a methionine/choline -deficient diet supplemented with 0.1% ethionine (MCDE), which causes the non-alcoholic steatohepatitis (NASH) that accompanies hepatic fibrosis (n=4 per group) 9. Compared with livers of chow-fed mice, livers of MCDE-fed mice contained significantly increased expression of fibrotic markers including vimentin, tgf-β, α-sma and col1α1 (Fig. 9a). [score:4]
In addition, we found evidence that expression of miR-378a-3p was regulated by Hh/NF-κB signalling. [score:4]
As expected, Gli3 at both the mRNA and protein levels was significantly downregulated in miR-378a-3p mimic -transfected cells, as analysed by qRT–PCR and western blotting (unpaired two-sample Student's t-test, P<0.05) (Fig. 4a–c). [score:4]
The degree of correlation between the expression levels of miR-378a-3p and gli3 in liver tissues of HCC and between the level of miR-378a-3p and hydroxyproline content or Gli3 in liver tissues of CCl [4] -treated mice were analysed by the Spearman's rank correlation coefficient (ρ). [score:3]
org) predicted that the miR-378 family targets human gli3 and gli2 mRNA and mouse gli3 and gli2 mRNA. [score:3]
We found that gli2 and gli3, downstream transcriptional factors of Hh signalling, were potential targets of miR-378a-3p, both in human and mouse, two species that share common miR-378a-3p seed sequences (Fig. 3a). [score:3]
Mutant vectors lacking the miR-378 -binding site were produced by site-directed mutagenesis using a QuikChange Site-Directed Mutagenesis Kit (Stratagene, Agilent) in accordance with the manufacturer's instructions. [score:3]
These findings indicate that miR-378a-3p has great potential to be used as a biomarker of hepatic pathogenesis and a therapeutic agent for treating liver disease. [score:3]
To identify the relevant target genes of the miR-378 family, we conducted bioinformatic analysis using http://www. [score:3]
N2a, a mouse neuroblastoma cell line, was co -transfected with a psiCHECK-2 vector containing either the wt or mut target sites plus either the miR-378a-3p mimic or the scrambled (Scr)-miR (control) oligonucleotide. [score:3]
In addition, expression of miR-378a-3p was higher in primary HSCs isolated from livers of mice treated with CCl [4]+NPs/M than in primary aHSCs (day 7) and almost similar to in primary qHSCs (day 0) (Fig. 7b). [score:3]
To investigate the potential role of miR-378a-3p in its clinical implications, we analysed the expression of miR-378a-3p and its target, gli3, in non-tumour and tumour regions of liver tissues obtained from 18 patients with hepatocellular carcinoma (HCC) and advanced fibrosis (stage F3 or F4). [score:3]
Therefore, we isolated primary aHSCs from CCl [4] -treated mice and transfected these cells with miR-378a-3p mimic or scrambled-miR (negative control), and then analysed the expression levels of genes related to HSC activation at 24 and 48 h after transfection. [score:3]
MiR-378 family was downregulated in injured livers of CCl [4] -treated mice. [score:3]
Microarray and qRT–PCR analyses showed that the expressional level of miR-378a-5p was not significantly changed in fibrotic liver, although it was transcribed together with miR-378 a-3p (Supplementary Fig. 3). [score:3]
Decreased expression of the miR-378 family in aHSCs. [score:3]
It is co-expressed with its host gene PGC-1β and constitutive activation of miR-378a in hepatocytes has been shown to prevent progression to hepatic fibrosis 28. [score:3]
In addition, we examined the expression of miR-378 family members in different types of liver cells, including hepatocytes, quiescent (day 0) HSCs (qHSCs) and liver sinusoidal endothelial cells (LSECs), primarily isolated from livers of normal mice. [score:3]
Smo influences expression of miR-378. [score:3]
Supplementary Fig. 13 shows that in qHSCs, the level of miR-378a-3p is high, so that miR-378a-3p blocks gli3, contributing to the lower expression of Gli3. [score:3]
Our results demonstrate that g li3 is a direct target of miR-378a-3p, as shown by bioinformatical analysis and luciferase reporter assay (Fig. 3). [score:3]
The expression of miR-378a-3p, miR-378b and miR-378d was also lower in primary aHSCs isolated from CCl [4] -treated mice than inactivated cells from corn-oil -treated mice (Fig. 2c). [score:3]
These findings suggest the possibility that miR-378a-3p and miR-378a-5p have disease-specific effects in liver. [score:3]
In the examination of liver of mice with or without NPs/NC, liver morphology and expression of genes, miR-378a-3p, gli3 and col1α1, were similar between two groups (Supplementary Fig. 11a,b). [score:3]
As expression of miR-378a-3p was decreased in the aHSCs and fibrotic liver tissue containing higher levels of gli3, we performed Spearman's rank correlation analysis to assess the degree of correlation between the levels of miR-378a-3p and gli3 in non-tumour and tumour liver tissue from individual HCC samples. [score:3]
As the aHSC is a major ECM-producing cell contributing to liver fibrosis 18 19, we examined the expression of miR-378 family members in LX2, a human aHSC line. [score:3]
A genetic variant in miR-378a DNA increases its promoter activity so that it acts as a tumour suppressor and leads to decreased susceptibility to HCC in the Chinese population 54. [score:3]
Expression of all of three miR-378 family members was reduced to a greater extent in LX2 than in HepG2, a human hepatocyte cell line (Fig. 2a). [score:3]
This activated p65 binds to the promoter (or control element) of the miR-378a gene, inhibiting its transcription. [score:3]
In parallel with Smo elevation, the expression of pri-miR-378a and miR-378a-3p in GDC-0449 -treated LX2 cells gradually decreased and was similar with it in vehicle -treated LX2 cells. [score:3]
NPs having miR-378a-3p increase the level of miR-378a-3p but decrease Gli3 expression in CCl [4] -treated mice. [score:3]
In TNF-α -treated LX2 cells, expression of miR-378a-3p was not significantly changed (data now shown). [score:3]
This decreased expression of the miR-378 family was validated in fibrotic livers of mouse mo dels with hepatic injury and also in aHSCs. [score:3]
Expression of miR-378a-3p and miR-378d was significantly lower in the MCDE-fed than the normal chow-fed mice at weeks 3 and 4 (unpaired two-sample Student's t-test, P<0.05). [score:3]
These findings suggest that expressional pattern of miR-378a-5p seems to be PSC specific. [score:3]
Target genes of human and mouse miR-378 were predicted by bioinformatic analysis using the online database http://www. [score:3]
In data analysis for the expression of miR-378a-3p and gli3 in human samples, average of expression of miR-378a-3p or gli3 from all paired non-tumour and tumour tissues was calculated. [score:3]
Expression of miR-378 declines in injured liver of MCDE-fed mice and of patients with HCC. [score:3]
Expression of miR-378 is reduced during HSC activation. [score:3]
In line with the findings of that study, our results demonstrated that expression of miR-378a-3p declined during liver fibrosis. [score:3]
Using Lipofectamine 2000 (Invitrogen), N2a cells were transfected with a mixture of psiCHECK-2 vector construct and either an miR-378a-3p mimic (25 nM; AccuTarget mouse miRNA-378a-3p mimic; Bioneer) or the same concentration of scrambled miRNA (miRNA mimic negative control 1; Bioneer) as a negative control. [score:3]
We found that miR-378a-3p, miR-378b and miR-378d were significantly downregulated at day 7 compared with day 0 of culture (Fig. 2b). [score:3]
Expression of all three miR-378 family member was greater in qHSCs than in primary LSECs (Fig. 2d). [score:3]
revealed that miR-378a-3p, not miR-378b or miR-378d, directly bound to gli3 but not gli2 mRNA, and that both of the two binding sites of the gli3 mRNA were active (Fig. 3c and Supplementary Fig. 4). [score:2]
These findings support the clinical implications of miR-378a-3p regulating Hh signalling in treating HCC. [score:2]
MiR-378a-3p suppresses activation of HSCs. [score:2]
MiR-378a-3p reduces expression of Gli3 and fibrosis in the liver. [score:2]
In addition, decreased expression of miR-378a-3p in these mice was significantly correlated with the degree of liver fibrosis, as assessed by hydroxyproline assay (Spearman's rank correlation analysis, r=−0.475, P=0.034, n=20) (Fig. 1d). [score:2]
This reduced expression of miR-378 family members was validated by real-time quantitative reverse transcriptase–PCR (qRT–PCR) analysis, which showed that miR-378a-3p was significantly decreased, and miR-378b and miR-378d tended to be reduced in fibrotic livers compared with controls (n=4 per group) both at 6 and 10 weeks (unpaired two-sample Student's t-test, P<0.05) (Fig. 1c). [score:2]
MiR-378a-3p induces inactivation of primary HSCs by reducing Gli3 and Gli2 expression. [score:2]
To examine how Smo is associated with p65 signalling in the transcriptional regulation of miR-378a-3p, we assessed whether p65 is activated by Smo. [score:2]
NP-encapsulated miR-378a-3p reduces hepatic damage. [score:1]
To examine the effect of miR-378 in vivo, 6-week-old mice received 0.4 ml kg [−1] body weight of CCl [4] (Sigma-Aldrich) dissolved in corn oil by i. p. injection, three times a week for 2 weeks 60 61. [score:1]
A previous study also reported that the miR-378 significantly declined in liver tissues of rat with dimethynitrosamine (DMN) -induced hepatic fibrosis 32. [score:1]
The data indicated that an upstream sequence of miR-378a, from nucleotides −820 to around −811, contained a putative binding site for NF-κB (p65), rather than Smo, at the 5′-region (Fig. 6a). [score:1]
In addition, the data from the human HCC samples support the correlation between miR-378a-3p and gli3. [score:1]
To evaluate the effect of miR-378 on HSC activation, LX2 cells (1.5 × 10 [5] per well) cultured for 24 h were transfected with 20 nM of miR-378 mimic (AccuTarget human miRNA-378a-3p mimic, Bioneer) or 20 nM of scrambled miRNA (miRNA mimic negative control 1, Bioneer) as a negative control using Lipofectamine RNAi/MAX transfection reagent (Invitrogen, Life Technologies, Carlsbad, CA, USA), according to the manufacturer's instructions. [score:1]
Next, mice were randomly divided into three experimental groups, which were treated with 0.4 ml kg [−1] body weight of CCl [4], twice a weeks for 3 weeks in parallel with once i. p. injection of PBS (CCl [4] group) or NP/M (6 nmol of miR-378a-3p mimic per mouse) or NP/NC (n=4 per group per week). [score:1]
In the present study, we focused on the action of miR-378a-3p associated with Hh signalling. [score:1]
NPs were formulated by blending LTU2a (197 mg dissolved in 9 ml of chloroform), copolymer of PEG-PLA (2 mg dissolved in 1 ml of chloroform) and linear polyethylenimine (LPEI) complexed with miRNA (100 nmol of miR-378a-3p or 100 nmol of scrambled miRNA at mass ratios of 5:1) or 2 mg of FITC–BSA (Sigma-Aldrich) dissolved in 1 ml of diethylpyrocarbonate (DEPC) -treated water using a water-in-oil-in-water emulsion and solvent evaporation 57 58. [score:1]
In line with their findings, miR-378a-3p, not the 5p, shows the significant changes in CCl [4] -treated mice and the association with HSC activation. [score:1]
We investigated expression differences of miR-378a-3p and gli3 between tumour and non-tumour liver tissues from patients with HCC and severe fibrosis. [score:1]
According to a database of microRNA TSS (miRStart), transcription start site is resided at −1,069 nucleotides (nt) on the miR-378a gene (chr5:149112388–149112453). [score:1]
The vector constructs with promoter region of primary (pri)-miR-378a were transformed into E. coli and then plasmid DNA was extracted from well-transformed and ampicillin-resistant E. coli using an AccuPrep Plasmid Mini Extraction Kit (Bioneer). [score:1]
Level of miR-378 declines in MCDE-fed mice and human HCC. [score:1]
During week 2 and 3, less than half the amount of miR-378a-3p was released but the persistence of release resulted in the gradual rise of the miR-378a-3p levels for each week post NP injection. [score:1]
MiR-378a-3p directly binds to Gli3 mRNA. [score:1]
The amount of gli3 mRNA was inversely correlated with the hepatic level of miR-378a-3p in those samples (r=−0.434, P=0.008, n=36) (Fig. 9d). [score:1]
However, our luciferase reporter assay showed that only miR-378a-3p, and not miR-378b or miR-378d, bound directly to the 3′-UTR region of gli3 mRNA in mouse (Fig. 3 and Supplementary Fig. 4). [score:1]
MiR-378 binds directly to Gli3. [score:1]
Mouse miR-378b and miR-378d have a similar sequence and structure to mouse miR-378a-3p, but a different seed sequence. [score:1]
In the current study, we found evidence for a new concept that miR-378a-3p and NF-κB signalling are involved in activation of Hh signalling during liver fibrosis. [score:1]
pGL3-basic vectors with (+p65BS) or without (Δp65BS) a p65 -binding site on the promoter region of pri-miR-378a were constructed. [score:1]
These results suggested that the miR-378 family is involved in HSC activation. [score:1]
In addition, levels of the miR-378 family were also low in injured livers of mice fed for 3 or 4 weeks on an MCDE diet. [score:1]
To deliver the miR-378a-3p into experimental animal mo del, LTU2a NPs encapsulated with miR-378a-3p mimic (NP/M) or scrambled miRNAs (NP/NC) as a negative control were prepared. [score:1]
The sequences of the miR-378 -binding sites of the 3′-UTR of gli3 and gli2 were confirmed by sequencing analysis (Macrogen, Seoul, Korea). [score:1]
These results suggested that miR-378a-3p mimic ameliorated chronic liver injury induced by CCl [4] in mice. [score:1]
Thus, the results of the luciferase reporter assay confirmed that p65 directly binds to the miR-378a gene (Fig. 6a). [score:1]
The control release of miR-378a-3p gradually normalizes the ALT and AST levels within 3 weeks after insults with CCl [4], even though only 6 μg mg [−1] of miR-378a-3p were released from the NPs after 1 week. [score:1]
To assess whether NPs/M were delivered into livers, the level of hepatic miR-378a-3p was examined by qRT–PCR analysis. [score:1]
The 3′-UTR of mouse gli3 and gli2, containing binding sites for mouse miR-378, were amplified by PCR using mouse gDNA. [score:1]
Data for in vivo effect of miR-378 in the liver were first analysed with the non-parametric Kruskal–Wallis test and then the differences between subgroups were further analysed by the two-sample Student's t-test. [score:1]
We investigated whether ectopic expression of miR-378a-3p in the aHSCs influenced HSC activation. [score:1]
Hence, using a prediction system, the TRANSFAC programme, we examined whether Smo might bind the gene of miR-378a. [score:1]
org), putative binding sites (red font) of miR-378a-3p were predicted in the 3′-UTR of gli2 and gli3 mRNA in mouse and human. [score:1]
To investigate whether activation of NF-κB signalling influences expression of miR-378a-3p, we treated cells with either an NF-κB signalling activator or repressor. [score:1]
The dashed line represents complementary base pairs between miR-378a-3p and gli2 or gli3 mRNA, whereas the grey shading indicates the seed sequence of miR-378a-3p. [score:1]
was conducted to assess the functional binding of p65 in this region of the miR-378a gene. [score:1]
The level of miR-378a-3p was lower in tumour tissues (0.82±0.185) than in non-tumour tissues (2.90±0.614), whereas gli3 mRNA level was higher in tumour tissues (6.98±1.991) than in non-tumour tissues (0.76±0.222) (Fig. 9c). [score:1]
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[+] score: 324
Other miRNAs from this paper: mmu-mir-378b, mmu-mir-378c, mmu-mir-378d
To clarify the roles of miRNA-378 in adiponectin gene expression, we evaluated variation in adiponectin, miRNA-378, and its related molecules, PPARγ [2] [13], [14], PGC-1β [13], [15], and estrogen-receptor-related receptor γ (ESRRG) [16] in white adipose tissue; second, we quantitated adiponectin level during adipogenesis in 3T3-L1 cells overexpressing the mimic or inhibitor of miRNA-378; finally, we assessed regulation of adiponectin expression by miRNA-378 in HEK293T cells expressing a luciferase-adiponectin-3'UTR sequence or a mutated construct. [score:10]
Representative blot (A), average expression levels of adiponectin protein (B) and Renilla-luciferase activity in HEK293T cells overexpressing the inhibitor or the mimic of miRNA-378 (C); Design of ΔmiR-378 binding site (BS) (D); Effects of overexpressing the mimic of miRNA-378R on the Renilla-luciferase activity in HEK293T cells with wild type or a deleted mutant of the miR-378 binding on 3′-UTR (E). [score:9]
0111537.g004 Figure 4 Representative blot (A), average expression levels of adiponectin protein (B) and in HEK293T cells overexpressing the inhibitor or the mimic of miRNA-378 (C); Design of ΔmiR-378 binding site (BS) (D); Effects of overexpressing the mimic of miRNA-378R on the in HEK293T cells with wild type or a deleted mutant of the miR-378 binding on 3′-UTR (E). [score:9]
Luminescence activity in HEK293T cells expressing a renilla-luciferase-adiponectin-3'UTR sequence was inhibited by overexpressing the mimic of miRNA-378, and the decrease was reversed by adding the inhibitor of miRNA-378. [score:9]
in HEK293T cells expressing the renilla-luciferase-adiponectin-3'UTR sequence was inhibited by overexpressing mimic of miRNA-378 and the decrease was partially reversed by adding the miRNA-378 inhibitor. [score:9]
Expression of ESRRG, alternatively targeted by miRNA-378, was also increased by miRNA-378 inhibitor and remarkably inhibited by mimic as previously reported by Eichner et al. [16]. [score:9]
We sought putative target sites for miRNAs in the 3'UTR of the adiponectin gene using TargetScan and PicTar and found that miRNA-378 could directly target the 3'UTR of adiponectin. [score:8]
After 3T3-L1 adipocytes were transfected with the miRNA-378 inhibitor/mimic from day 4 through day 6, adiponectin expression was seen to be increased by the inhibitor and repressed by the mimic (Figure 4 ). [score:7]
It is interesting that upregulation of miR-378 and downregulation of adiponectin by TNFα mimic the phenotype of diabetic ob/on mice [23]. [score:7]
Addition of TNFα led a significant upregulation of miR-378 (Figure 5A ) and downregulation of adiponectin at mRNA and protein levels (Figure 5A & 5B ). [score:7]
Addition of tumor necrosis factor-α (TNF α) led a upregulation of miR-378 and downregulation of adiponectin at mRNA and protein levels in 3T3-L1 cells. [score:7]
To determine whether adiponectin expression was directly regulated by miRNA-378, we measured the effects of the inhibitor or mimic of miRNA-378 on renilla-luciferase activity in HEK293T cells expressing a renilla-luciferase-adiponectin-3'UTR sequence. [score:7]
The expression of adiponectin was not significantly increased by miRNA-378 inhibitor but remarkably inhibited by mimic (p<0.01). [score:7]
In silico prediction of miRNA-378 targetsTo predict miRNA-378 targets, we used TargetScan (www. [score:7]
was inhibited by overexpressing the mimic of miRNA-378, and the decrease was partially reversed by adding the miRNA-378 inhibitor. [score:7]
To confirm that miRNA-378 is crucial for the expression of adiponectin, and if so, how it regulates adiponectin expression, we performed the in vitro experiments described above. [score:6]
Overexpression and knockdown of miRNA-378 were done by transfecting miScript miRNA-378 mimic (pre-mir) and/or inhibitor (anti-sense) (QIAGEN) with RNAiMax transfection reagent (Life Technologies) on day 4 according to the manufacturer's instruction. [score:6]
To assess whether or not the putative miR-378 binding site was effectively utilized to regulate the expression of adiponectin, we transfected a renilla-luciferase-adiponectin-3'UTR sequence to HEK293T cells and further transfected the mimic and inhibitor of miRNA-378 (Figure 4C ). [score:6]
On day 4, overexpression and knockdown of miRNA-378 were done by transfecting the miRNA-378 mimic and/or inhibitor. [score:6]
Since the inhibitory effects of the mimic were cancelled in a deleted mutant of the miR-378 3′-UTR binding site (Figure 4D & 4E), suggesting that the regulation of adiponectin expression by miR378 can occur via the adiponectin-3'UTR sequence. [score:6]
They subsequently showed that overexpression of miRNA-378 upregulated a set of lipogenic genes, suggesting the involvement of PPARγ [2] machinery [13]. [score:6]
As shown, expression levels of miRNA-378 were effectively decreased by the inhibitor (p<0.05) and increased by the mimic (p<0.01). [score:5]
Second, the results from a mo del overexpressing a miRNA-378 mimic/inhibitor may not be relevant to natural physiological systems. [score:5]
Overexpressing the mimic or inhibitor of miRNA-378. [score:5]
By searching in silico, we found a putative target site for miRNA-378 in the 3 prime untranslated region (3'UTR) of the adiponectin gene (Adipoq). [score:5]
Levels of miRNA-378, adiponectin, PPARγ [2], PGC1α, ESRRG, PGC1β, ACSL1 and AGPAT6 in 3T3-L1 adipocytes overexpressing the inhibitor (inh) or mimic (mim) of miRNA-378. [score:5]
First, we determined a putative target site for miRNA-378 in the 3 prime untranslated region (3'UTR) of the adiponectin gene by in silico analysis. [score:5]
0111537.g003 Figure 3Levels of miRNA-378, adiponectin, PPARγ [2], PGC1α, ESRRG, PGC1β, ACSL1 and AGPAT6 in 3T3-L1 adipocytes overexpressing the inhibitor (inh) or mimic (mim) of miRNA-378. [score:5]
The mimic and inhibitor of miRNA-378 had little or no effect on expression of PPARγ [2], PGC1α, PGC1β, and AGPAT6, but the mimic decreased ACSL1 (p<0.05) significantly. [score:5]
First, we sought putative target sites for miRNAs in the 3'UTR of the adiponectin gene and found that miRNA-378 could target that region. [score:5]
Gerin et al. reported that overexpression of miR-378 leads to increased lipid droplet size, lipogenesis, and expression of PPARγ [2] and Glut4 [13]. [score:5]
Although the repressive influence of miRNA-378 on the adiponectin gene likely contributes to the lowering of adiponectin expression, the combined effects of the miRNA on multiple target genes might be involved [13], [15], [16], [22]. [score:5]
To predict miRNA-378 targets, we used TargetScan (www. [score:5]
In 3T3-L1 cells, both adiponectin and miR-378 are increased during differentiation into adipocytes, suggesting that miR-378 is not a suppressor of adiponectin mRNA expression during normal differentiation. [score:5]
The miRNA-378 targets were predicted using Targetscan (www. [score:5]
Next, we evaluated the effects of overexpressing mimic or inhibitor of miRNA-378 on the expression of adiponectin, PPARγ [2], PGC1α, ESRRG, PGC1β, ACSL1, and AGPAT6 (Figure 3 ). [score:5]
We analyzed that an inflammatory cytokine, TNFα, which is known as a negative regulator for adiponectin [6], may alter levels of miR-378 expression in 3T3-L1 adipocytes (Figure 5 ). [score:4]
From the current study, it is not clear why miR-378 is upregulated by TNFα. [score:4]
Taken together, miR-378 could play a role in pathophysiological conditions via the regulation of adiponectin expression discussed below. [score:4]
It might be suggested that miR-378 regulates adiponectin expression in a pathological condition. [score:4]
Taken above, miR-378 might regulate adiponectin expression through a C/EBP binding site of the adiponectin promoter [13]. [score:4]
Simultaneously, mRNA for PGC-1β, which contains an RNA hairpin that generates miRNA-378, and that for ESRRG, which is one of the nuclear receptors coactivated by PGC-1β and is targeted by miRNA-378 at two regions within the 3'UTR, increased during preadipocyte differentiation. [score:3]
Prediction of miRNA-378 targets in silico. [score:3]
Second, we found that intracellular levels of miRNA-378 were crucial in determining adiponectin expression, and that miRNA-378 could modulate adiponectin levels via the 3'UTR sequence -binding site. [score:3]
Moreover, miRNA-378 has been shown to target mRNAs encoding ESRRG and GA -binding protein-α, which associates with PGC-1β to control oxidative metabolism [16]. [score:3]
0111537.g001 Figure 1Prediction of miRNA-378 targets in silico. [score:3]
HEK293T cells were dispensed into 24-well or 96-well plates and co -transfected with psiCheck2 (Promega) carrying the Adipoq 3′UTR or ΔmiR-378 binding site (BS) (0.5 µg/well in a 24-well plate or 0.2 µg/well in a 96-well plate) and mimic or inhibitor of miRNA-378 using RNAiMax (Life Technologies) as per the manufacturer's protocol. [score:3]
Moreover, we confirmed the inhibitory effects of the mimic were cancelled in a deleted mutant of the miR-378 3′-UTR binding site (Figure 4D & 4E). [score:3]
In silico prediction of miRNA-378 targets. [score:3]
The levels of adiponectin mRNA and protein were decreased in 3T3-L1 cells overexpressing the mimic of miRNA-378. [score:3]
In conclusion, expression of adiponectin can be modulated by miR-378 via the 3'UTR miRNA-378 binding site. [score:3]
Moreover, we confirmed the inhibitory effects of the mimic were cancelled in a deleted mutant of the miR-378 3′-UTR binding site. [score:3]
During differentiation, expression of miRNA-378 and adiponectin were increased. [score:3]
We found that levels of miRNA-378 could modulate adiponectin expression via the 3'UTR sequence -binding site. [score:3]
Searching in silico, we found a putative target site for miRNA-378 in the 3'UTR of the adiponectin gene (Figure 1 ). [score:3]
In this study, we evaluated whether the miRNA-378 pathway is involved in regulation of adiponectin expression. [score:2]
and site-directed mutagenesisWe transfected the mimic and inhibitor of miR-378 into differentiating 3T3-L1 cells on day 4 and evaluated the levels of adiponectin protein on day 6 (Figure 4A & 4B ), indicating that the mimic reduced adiponectin levels almost by half. [score:2]
To detect miRNA-378 and U6 RNA polymerase (as an internal control) expression levels, we used the TaqMan MicroRNA Reverse Transcription Kit and TaqMan primer/probe sets for miRNA-378 and U6 (Applied Biosystems), respectively, as per their protocols. [score:2]
We evaluated whether the miRNA-378 pathway is involved in regulating adiponectin expression. [score:2]
In our C57BL/6 and ob/ob study, level of miR-378 was positively correlated with lipogenic molecules such as PPARγ [2], PGC1α, ESRRG and AGPAT and also with a negative regulator for adiponectin, TNFα. [score:2]
All data were analyzed by the ΔΔCt method, using β-actin (for genes) or U6 (for miR-378) as internal controls, respectively. [score:1]
The above vector construct was further mutagenized to introduce point mutations to delete miR-378 binding sites with High Fi delity Phusion polymerase and primers, AAATAATTTGTGTTCCTA gaattcAAAAAAAGGCACTCCC (Forward, EcoRI site in underlined) and GGGAGTGCCTTTTTTT gaattc TAGGAACACAAATTATTT (reverse). [score:1]
Carrer et al. showed that mice genetically lacking miRNA-378 are resistant to obesity induced by a high-fat diet, and exhibit enhanced mitochondrial fatty acid oxidation [15]. [score:1]
Level of miR-378 was higher and mRNA level of adiponectin was lower in diabetic ob/ob mice than those of normal C57BL/6 mice and levels of miR378 and adiponectin were negatively well correlated (r = −0.624, p = 0.004). [score:1]
0111537.g002 Figure 2Levels of miRNA-378, adiponectin, PPARγ [2], PGC1α, ESRRG, PGC1β, ACSL1 and AGPAT6 during differentiation of 3T3-L1 adipocyte cells. [score:1]
Levels of miRNA-378, adiponectin, PPARγ [2], PGC1α, ESRRG, PGC1β, ACSL1 and AGPAT6 during differentiation of 3T3-L1 adipocyte cells. [score:1]
They further described that miR-378 induces transactivation of C/EBP, indicating that miR-378 can act through a mechanism independent of the classical miRNA machinery. [score:1]
Level of miR-378 was higher and level of adionectin was lower in ob/ob mice than those of C57BL/6. [score:1]
All these above researches on miR-378 and metabolic events were demonstrated in rodent mo dels so far, in future our findings warrant further investigations into the role of miRNA-378 and other miRNAs possibly affecting the adiponectin expression in human subjects, which is linked to metabolic and cardiovascular abnormalities associated with obesity and insulin resistance. [score:1]
Level of miR378 was negatively correlated with mRNA levels of adiponectin. [score:1]
Level of miR378 was positively correlated with PPARγ [2], PGC1α, ESRRG and TNFα, but not with levels of ACSL1 and AGPAT6 (Figure 7 ). [score:1]
Correlation between level of miRNA-378 vs levels of adiponectin, PPARγ [2], PGC1α, ESRRG, PGC1β, ACSL1, AGPAT6 and TNFα in the adipose tissue of C57BL/6 and ob/ob mice. [score:1]
To investigate the effects of miRNA-378 on the expression levels of adiponectin, we performed in vitro experiments, beginning by analyzing the abundance of miRNA-378 and adiponectin-related molecules during preadipocyte differentiation in 3T3-L1 cells, using qRT-PCR (Figure 2 ). [score:1]
3T3L1 adipocytes were treated with human recombinant TNFα (10 µg/mL, R&D systems) on day 6 and miR-378 and mRNA levels were evaluated by qRT-PCR or on day 7. Expression levels normalized to those of β-actin. [score:1]
miRNA-378 in C57BL/6 and ob/ob mice. [score:1]
miRNA-378 -mediated repression of carnitine O-acetyltransferase (CRAT) [15], a mitochondrial enzyme involved in fatty acid oxidation, and MED13, a component of the mediator complex that controls nuclear hormone receptor activity [15], and insulin-like growth factor 1 receptor [22], might at least partly contribute, to the elevated oxidative capacity. [score:1]
miRNA-378 in 3T3-L1 adipocytes. [score:1]
Levels of miRNA-378, adiponectin, PPARγ2, PGC1α, ESRRG, PGC1β, ACSL1, AGPAT6 and TNFα in the adipose tissue of C57BL/6 and ob/ob mice. [score:1]
We transfected the mimic and inhibitor of miR-378 into differentiating 3T3-L1 cells on day 4 and evaluated the levels of adiponectin protein on day 6 (Figure 4A & 4B ), indicating that the mimic reduced adiponectin levels almost by half. [score:1]
0111537.g007 Figure 7Correlation between level of miRNA-378 vs levels of adiponectin, PPARγ [2], PGC1α, ESRRG, PGC1β, ACSL1, AGPAT6 and TNFα in the adipose tissue of C57BL/6 and ob/ob mice. [score:1]
To explore the function of miR378 on the pathological conditions, we stimulated 3T3-L1 adipocyte with human recombinant TNFα (10µg/mL, R&D systems) on day 6 and levels of adiponectin expression were evaluated by quantitative reverse transcription PCR (qRT-PCR) or. [score:1]
TNFα and miR378. [score:1]
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Compared with primary hepatocytes isolated from quiescent livers (0 h), Smo mRNA levels in hepatocytes from PH given mice were maintained at basal levels until 12 h, then began to increase, showing significant upregulation at 48 and 72 h. MiR-378 expression showed consistent reduction, below 40% of basal levels, whereas the expression of Gli3 targeted by miR-378 [22] tended to increase gradually, with significant upregulation at 48 and 72 h. Expression of Tgfb and Snail gradually increased and showed the plateau after presenting the significant elevation at 12 h. Vimentin was upregulated at 24 h, peaking at 72 h, while E-cadherin was downregulated at 24 h and restored to nearly its basal level at 48 h (Fig.   1a). [score:20]
To inhibit the expression of miR-378 in both primary hepatocytes and AML12, cells were transfected with 75 nM or 100 nM of miR-378 inhibitor (AccuTarget™ mouse miRNA-378a-3p inhibitor, Bioneer), respectively, using Lipofectamine RNAi/MAX transfection reagent (Invitrogen, Thermo Fisher Scientific) according to the manufacturer’s instructions. [score:11]
Smo was slightly upregulated at 3 h, rapidly downregulated at 6 h, and then tended to increase gradually until 96 h. MiR-378 inhibited by SMO revealed the opposite expression pattern with Smo. [score:10]
Because most downregulation of miR-378a, upregulation of other genes and cell proliferation were observed in both livers and hepatocytes at 72 h post-PH in our analysis, we assessed the expression of miR-378 and EMT-related genes at this time point. [score:9]
MiR-378 showed lowered expression at 3 h, then began to elevate, peaking at 12 h, then gradually decreasing until 96 h. Expression of Gli3 targeted by miR-378 greatly increased at 6 h, similar to the pattern of Smo, and declined to below basal levels at 12 h, the point at which miR-378 was highly expressed. [score:9]
The upregulated Smo, Gli3, p65, Tgfb, Snail, and Vimentin, and the downregulated miR-378 and E-cadherin in AAV8-TBG-GFP -treated PH liver were reversed in AAV8-TBG-Cre -treated PH liver, presenting the impaired EMT in PH liver with Smo suppression (Fig.   5c). [score:9]
The upregulated Smo, Gli3, p65, Tgfb, Snail, and Vimentin, and the downregulated miR-378 in PH liver with NC were reversed in PH liver with miR-378 mimic, presenting the alleviation of these Hh-target and EMT-related genes, and the elevation of miR378 (Fig.   7). [score:9]
Given that Hh signaling orchestrates EMT in the liver-repair process 5, 13 and that miR-378 targeting GLI3 influenced the transition of HSCs, with expression regulated by SMO [22], we examined the expression of miR-378, Smo, and Gli3 in regenerating livers. [score:8]
Their expressional changes were reverse in hepatocytes from miR-378 mimic -transfected PH liver, displaying the downregulation of Hh-activators and EMT-promoting genes and the upregulation of miR-378 and E-cadherin compared with NC -transfected hepatocytes from PH livers (Fig.   8a). [score:8]
EMT-favorable genes, including Smo, Gli3, p65, Tgfb, Snail, and Vimentin were significantly downregulated, whereas the EMT-inhibiting genes, miR-378 and E-cadherin, were significantly upregulated in AdCre -treated hepatocytes from Smo- flox mice with PH (black bar), compared to the AdGFP -treated hepatocytes from Smo- flox mice with PH (white bar) (Fig.   4a). [score:8]
Although miR-378 expression was inversely correlated with expression of Smo and Gli3 in collected liver remnants at various times during liver regeneration, downregulation of miR-378 in hepatocytes from PH livers was observed earlier than increase in Smo, suggesting that other factors might be involved in the miR-378 reduction. [score:8]
Compared to miR-378 expression in AML12 cells treated with or without the NC, its level was successfully reduced, followed by elevated expression of Gli3 in AML12 cells with miR-378 inhibitor at 12 or 24 h. Levels of mesenchymal markers, Tgfb, Snail, Vimentin and Col1a1 were significantly elevated in miR-378 inhibitor -treated AML12 cells, whereas the levels of epithelial markers, including E-cadherin and Zo-1 were significantly alleviated in these cell, compared with two control groups (Supplementary Figure  S5). [score:7]
In addition, p65 levels declined, followed by upregulation of miR-378 and downregulation of GLI3 in Smo- deleted hepatocytes (Fig.   4), indicating that SMO is an essential factor linking miR-378 with the Hh signaling pathway in promoting EMT. [score:7]
Protein data also confirmed the RNA data by presenting higher expression of SMO and VIMENTIN and lower expression of E-cadherin in miR-378 suppressed hepatocytes than the other groups (Fig.   3b). [score:7]
The RNA level of p65 was also inversely correlated with miR-378 expression in hepatocytes from PH liver at various times (r = −0.469, p = 0.024), although p65 RNA tended to be upregulated at 3 h and began to be raised significantly at 24 h (data not shown). [score:6]
The mRNA levels of E-cadherin were downregulated in miR-378 inhibitor -treated hepatocytes, compared to other groups. [score:5]
Increased expressions of Smo, Gli3, p65, Tgfb, Snail, and Vimentin and decreased expressions of miR-378 and E-cadherin in hepatocytes from AAV8-TBG-GFP -treated PH livers were reversed in cells from AAV8-TBG-Cre -treated PH livers (Fig.   6a). [score:5]
Overexpression of miR378 impedes liver regeneration in mice by suppressing hepatocyte EMT. [score:5]
To verify this hypothesis, we suppressed miR-378 in quiescent hepatocytes and assessed the expression of EMT-related genes in these cells. [score:5]
Fig. 3 a qRT-PCR of miR-378, Gli3, Tgfb, Snail, Col1a1, Vimentin and E-cadherin in primary hepatocytes (pHEP), which were isolated from WT mice and transfected with miR-378 inhibitor (I, 75 nM, diagonal lined bar) or scramble miR (NC, 75 nM, white bar) for 12 and 24 h. All results of relative expression values are shown as mean ± s. e. m. of triplicate experiments (unpaired two-sample Student’s t test, * p < 0.05 ** p < 0.005 vs. [score:5]
Because p65 was reported to be activated by Smo and to inhibit miR-378 transcription [22], p65 expression was examined. [score:5]
both cells cultured alone (black bar) and cultured with NC) a qRT-PCR of miR-378, Gli3, Tgfb, Snail, Col1a1, Vimentin and E-cadherin in primary hepatocytes (pHEP), which were isolated from WT mice and transfected with miR-378 inhibitor (I, 75 nM, diagonal lined bar) or scramble miR (NC, 75 nM, white bar) for 12 and 24 h. All results of relative expression values are shown as mean ± s. e. m. of triplicate experiments (unpaired two-sample Student’s t test, * p < 0.05 ** p < 0.005 vs. [score:5]
Expressional changes of miR-378 with Hh-target genes in regenerating livers. [score:5]
Expressional changes of miR-378, Hh target genes, and EMT activator in hepatocytes from mice with PH. [score:5]
The mRNA levels of Gli3, Tgfb, Snail, Col1a1, and Vimentin were upregulated following miR-378 reduction in miR-378 inhibitor -treated hepatocytes, compared to primary hepatocytes treated with or without the NC (Fig.   3a). [score:5]
These data demonstrate that miR-378 is involved in hepatocyte EMT by suppressing Gli3 expression. [score:5]
Given that miR-378 influences GLI3 expression in the liver repair process [22] and the expressional changes of EMT-related and Hh-target genes were observed in PH livers, we investigated whether hepatocytes undergo an EMT and whether miR-378 -mediated Hh signaling contributes to this process. [score:5]
Prior work demonstrated that p65 activated by SMO -suppressed miR-378 expression in HSCs, contributing to HSC activation and liver fibrosis [22]. [score:5]
Protein analysis also confirmed the RNA data by presenting decreased expression of SMO, GLI3, VIMENTIN and SNAIL and increased expression of E-cadherin in hepatocytes from miR-378 mimic -treated PH liver compared with cells from NC -treated PH liver (Fig.   8b). [score:4]
MiR-378 expression was inversely correlated with the Hh-target genes, Smo and Gli3, and the EMT-related genes, Tgfb, Snail and Vimentin, in hepatocytes from mice PH livers (Fig.   1b). [score:4]
Taken together, these results demonstrate that SMO is a master regulator of EMT in hepatocytes by altering miR-378 expression during liver regeneration. [score:4]
Hyun J MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expressionNat. [score:4]
0 h) We found that hepatocytes underwent EMT and the higher level of miR-378 in quiescent hepatocytes was significantly downregulated in hepatocytes undergoing EMT. [score:4]
In line with data of gene expression in PH liver transfected with miR-378 or NC, primary hepatocytes from NC -treated mice with PH at 72 h had the higher level of Smo, Gli3, p65, Tgfb, Snail, and Vimentin, and the lower level of miR-378 and E-cadherin than hepatocytes from NC -treated mice without PH. [score:3]
PH with NC)To assess whether the impeded liver regeneration in miR-378 mimic -treated mice resulted from the suppressed EMT in hepatocytes, the levels of miR-378 and EMT-related genes were examined in hepatocytes isolated from these mice. [score:3]
The degree of correlation between the expression levels of miR-378a-3p and Smo, Gli3, Tgfb, Snail, and Vimentin in primary hepatocytes isolated from PH liver was analyzed by the Pearson’s correlation coefficient. [score:3]
AML12, a murine cell line of normal hepatocytes, was transfected with miR-378 inhibitor or scrambled miR as negative control (NC). [score:3]
PH with NC) To assess whether the impeded liver regeneration in miR-378 mimic -treated mice resulted from the suppressed EMT in hepatocytes, the levels of miR-378 and EMT-related genes were examined in hepatocytes isolated from these mice. [score:3]
However, these enzymatic levels were significantly higher and Ki67 -expressing cells were less obvious in miR-378 mimic -treated liver than two control groups (Fig.   7a, b). [score:3]
All results of relative expression values are shown as mean ± s. e. m. of triplicate experiments (one-way ANOVA with Tukey corrections, * p < 0.05 ** p < 0.005) a qRT-PCR for Smo, miR-378, Gli3, p65, Tgfb, Snail, Vimentin and E-cadherin in primary hepatocytes, which were isolated from AAV8-TBG-GFP or AAV8-TBG-Cre -treated mice with (PH) or without PH (nonPH) (N = 3 per group). [score:3]
Fig. 1 a Expression of Smo, miR-378, Gli3, Tgfb, Snail, Vimentin, and E-cadherin was assessed by qRT-PCR analysis in primary hepatocytes isolated from mice at 3, 6, 12, 24, 48 and 72 h after PH. [score:3]
b Pearson’s correlation coefficient between miR-378 expression and Smo, Gli3, Tgfb, Snail, and Vimentin (N = 24, Pearson’s correlation r = −0.435, p = 0.034 with Smo; r = −0.531, p = 0.009 with Gli3; r = −0.547, p = 0.01 with Tgfb; r = −0.578, p = 0.003 with Snail; r = −0.484, p = 0.019 with Vimentin) a analysis for SMO (86 kDa), nuclear GLI3 (145 kDa) and p65 (65 kDa), processed form of TGFb (25 kDa ), VIMENTIN (57 kDa), αSMA (42 kDa ), E-cadherin (120 kDa), GAPDH (36 kDa), and LAMINb1 (68 kDa) in primary hepatocytes isolated from PH livers of mice. [score:3]
Interestingly, regardless of PH, Smo expression was lower and miR-378 level higher in the AAV8-TBG-Cre than the AAV8-TBG-GFP group (Figs.   5 & 6). [score:3]
0 h) a Expression of Smo, miR-378, Gli3, Tgfb, Snail, Vimentin, and E-cadherin was assessed by qRT-PCR analysis in primary hepatocytes isolated from mice at 3, 6, 12, 24, 48 and 72 h after PH. [score:3]
b Pearson’s correlation coefficient between miR-378 expression and Smo, Gli3, Tgfb, Snail, and Vimentin (N = 24, Pearson’s correlation r = −0.435, p = 0.034 with Smo; r = −0.531, p = 0.009 with Gli3; r = −0.547, p = 0.01 with Tgfb; r = −0.578, p = 0.003 with Snail; r = −0.484, p = 0.019 with Vimentin) Fig. 2 a analysis for SMO (86 kDa), nuclear GLI3 (145 kDa) and p65 (65 kDa), processed form of TGFb (25 kDa ), VIMENTIN (57 kDa), αSMA (42 kDa ), E-cadherin (120 kDa), GAPDH (36 kDa), and LAMINb1 (68 kDa) in primary hepatocytes isolated from PH livers of mice. [score:3]
MiR-378 suppressed hepatocyte EMT. [score:2]
Taken together, these results suggest that miR-378 is involved in liver regeneration by regulating EMT in hepatocytes. [score:2]
MiR-378 suppresses hepatocyte EMT in mice with PH. [score:2]
Since primary cells better reflect the physiological state of cells in vivo compared to cell lines, we isolated hepatocytes primarily from livers of WT mice and transfected them with miR-378 inhibitor or scramble miR. [score:2]
MiR-378 inhibitor promotes EMT in primary hepatocytes of mice. [score:2]
Taken together, these findings suggest miR-378 as an important regulator for hepatocyte transdifferentiation in regenerating livers. [score:2]
Fig. 7 a Images, H & E-, and Ki67-stained sections of livers from miR-378 mimic- or scramble RNA- (negative control: NC) transfected mice with (N = 5 per group) or without PH (N = 3 per group). [score:1]
Given that Hh signaling is associated with the fate-change of hepatocytes and HSCs in the liver-repair process, it is possible that miR-378–mediating Hh signaling influences the EMT of hepatocytes in regenerating livers after PH. [score:1]
We recently demonstrated that miR-378 is involved in HSC transition in the fibrotic liver by interacting Hh signaling [22]. [score:1]
These findings indicate that EMT occurs in regenerating liver and SMO-GLI3-miR-378 axis is associated with this process. [score:1]
Fig. 6 a qRT-PCR for Smo, miR-378, Gli3, p65, Tgfb, Snail, Vimentin and E-cadherin in primary hepatocytes, which were isolated from AAV8-TBG-GFP or AAV8-TBG-Cre -treated mice with (PH) or without PH (nonPH) (N = 3 per group). [score:1]
Immunoblots shown represent one of three independent experiments with similar results a qRT-PCR for Smo, miR-378, Gli3, p65, Tgfb, Snail, Vimentin, and E-cadherin in primary hepatocytes. [score:1]
To examine the effect of miR-378 in vivo, in vivo-jetPEI (Polyplus Transfection, Illkirch, France) was used according to the manufacturer’s protocols. [score:1]
Fig. 8 a qRT-PCR for Smo, miR-378, Gli3, p65, Tgfb, Snail, Vimentin, and E-cadherin in hepatocyte which were isolated from PH or quiescent liver and transfected with miR-378 mimic (PH with miR378: diagonal lined bar) or NC (nonPH with NC: white bar/ PH with NC: black bar). [score:1]
Liver regeneration is impaired in miR-378 mimic -transfected mice. [score:1]
The results suggested that hepatocytes undergo EMT after PH, and Hh activators and miR-378 are associated with this process during liver regeneration. [score:1]
In addition, our findings demonstrated that hepatocytes undergo EMT and the Hh signaling -mediated miR-378 is involved in this process during liver regeneration of PH -treated mice. [score:1]
c qRT-PCR for Smo, miR-378, Gli3, p65, Tgfb, Snail, and Vimentin in livers of these mice. [score:1]
Hence, we examined whether p65 induced the earlier reduction of miR-378 in hepatocytes from PH liver. [score:1]
Smo plays the major role in the miR-378 -mediated EMT in hepatocytes. [score:1]
8-week-old male C57BL/6 WT mice were injected intraperitoneally (i. p. )with 6 nmol per mice of miR-378 mimic (N = 5) or scramble miRNA (N = 5) (Bioneer) as a negative control 12 h before PH. [score:1]
Fig. 4 a qRT-PCR for Smo, miR-378, Gli3, p65, Tgfb, Snail, Vimentin, and E-cadherin in primary hepatocytes. [score:1]
PH with NC) a Images, H & E-, and Ki67-stained sections of livers from miR-378 mimic- or scramble RNA- (negative control: NC) transfected mice with (N = 5 per group) or without PH (N = 3 per group). [score:1]
We found that reduced miR-378 leads to the activation of Hh signaling which is involved in EMT in regenerating liver. [score:1]
Therefore, our findings demonstrate that hepatocytes experience EMT during liver regeneration and miR-378 is involved in this process through interfering with the Hh pathway, particularly the SMO-GLI3 axis. [score:1]
The RNA levels of Smo, miR-378, Gli3, and EMT-markers, were similar between these two groups of cells from quiescent liver (Supplementary Figure  S6A). [score:1]
Hence, it is possible that miR-378 prevents hepatocytes from undergoing EMT. [score:1]
Mean ± s. e. m. results are graphed (one-way ANOVA with Tukey corrections, * p < 0.05 ** p < 0.005) (c) qRT-PCR for Smo, miR-378, Gli3, p65, Tgfb, Snail, Vimentin and E-cadherin in these livers. [score:1]
PH with NC) a qRT-PCR for Smo, miR-378, Gli3, p65, Tgfb, Snail, Vimentin, and E-cadherin in hepatocyte which were isolated from PH or quiescent liver and transfected with miR-378 mimic (PH with miR378: diagonal lined bar) or NC (nonPH with NC: white bar/ PH with NC: black bar). [score:1]
Our data also indicate that miR-378 is associated with EMT in hepatocytes of PH livers. [score:1]
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Other miRNAs from this paper: mmu-mir-378b, mmu-mir-378c, mmu-mir-378d
Firstly, at both mRNA and protein level, up-regulation of miR-378 expression in SW620 cells effectively suppressed vimentin expression, whereas, downregulation of miR-378 moderately promoted vimentin expression. [score:15]
To further confirm that vimentin is the direct target of miR-378, we first determined whether over -expression of miR-378 can lead to down-regulation of vimentin expression. [score:11]
Over -expression of miR-378 inhibited SW620 cell growth and invasion, and resulted in down-regulation of vimentin expression. [score:10]
However, other studies demonstrated that miR-378 was down-regulated in gastric cancer and oral cancer [11, 16], and miR-378 may act as tumor suppressors in gastric cancer by negatively regulating the expression of CDK6 and VEGF [16]. [score:9]
Taken together, these findings sufficiently consolidated that miR-378 played a suppressive role in cellular proliferation and invasion, at least, in part due to directly inhibiting vimentin expression. [score:8]
In the current study, we further confirmed that miR-378 expression was significantly down-regulated in CRC tissue samples and cell lines, and that loss of miR-378 expression was associated with large tumor size, advanced clinical stage, lymph node metastasis and shorter overall survival of the patients with CRC, indicating that miR-378 might be involved in CRC progression and could be used as a potential prognostic biomarker in CRC. [score:8]
Thus, vimentin is likely to be suppressed by miR-378 through translational inhibition and mRNA degradation. [score:7]
Inversely, down-regulation of miR-378 in inhibitors transfected SW620 cells apparently promoted cell invasion (Figure  3D). [score:6]
In addition, we further identified vimentin as the functional downstream target of miR-378 by directly targeting the 3′-UTR of vimentin. [score:6]
Relatively, down-regulation of miR-378 by inhibitors in SW620 cells led to a moderate increase of vimenin protein level (Figure  5B). [score:6]
In conclusion, miR-378 may function as a tumor suppressor and plays an important role in inhibiting tumor growth and invasion. [score:5]
Furthermore, over -expression of miR-378 could significantly inhibit cell proliferation and invasion in vitro and tumor growth in vivo. [score:5]
To understand the possible mechanisms that might underlie miR-378 -mediated growth and metastasis suppression, we performed in silico studies to search for potential gene targets of miR-378 using the bioinformatics algorithms Pictar and miRanda. [score:5]
It showed that the increased expression of miR-378 induced significant inhibition on cell proliferation (Figure  3A). [score:5]
Moreover, patients with low miR-378 expression had significantly poorer overall survival, and miR-378 expression was an independent prognostic factor in CRC. [score:5]
We also found that miR-378 can inhibit tumor growth and invasion partly by targeting vimentin. [score:5]
To explore the mechanisms underlying the inhibition of CRC cell growth and invasion mediated by miR-378, we next set out to identify the potential target genes of miR-378. [score:5]
However, miR-378 knock-down promoted these processes and enhanced the expression of vimentin. [score:4]
We transfected SW620 cells with pre-miR-378 or anti-miR-378, Western blot showed that the enhanced miR-378 expression in SW620 cells significantly repressed vimentin protein expression compared to cells transfected with scramble control (Figure  5B). [score:4]
To directly address whether miR-378 binds to the 3′-UTR of target mRNA, we generated a luciferase reporter vector that contain the vimentin 3′-UTR with the putative miR-378 binding sites. [score:4]
We compared the clinicopathological factors of the high and low miR-378 expression group (Table  1) and found that low expression of miR-378 was significantly correlated with large tumor size (P = 0.035), positive lymph node metastasis (P = 0.004), and advanced clinical stage (P = 0.017). [score:4]
In this study, we confirmed that miR-378 significantly down-regulated in CRC cancer tissues and cell lines. [score:4]
Several studies have been reported that miR-378 was significantly down-regulated in CRC [17-20]. [score:4]
Taken together, these findings indicate that vimentin is a direct, downstream target for miR-378 in SW620 cells. [score:4]
Vimentin is a direct target of miR-378. [score:4]
Previous reports revealed that the miR-378 was down-regulated in CRC [17- 20]. [score:4]
Several pieces of evidence in our study indicate that vimentin is a direct target gene of miR-378 in CRC cancer. [score:4]
In these types of cancer, miR-378 seemed to be an oncogene, and enhanced tumor cell survival, promoted tumor growth and metastasis in some tumors via regulation of the target genes SuFu, Fus-1, HMOX1, ESRRG and GABPA [12- 15]. [score:4]
Accumulating evidence showed that up-regulation of miR-378 was associated with several types of human malignant solid tumors, including those of the glioblastoma, breast cancer and renal cell carcinoma [12, 13, 15]. [score:4]
However, the specific mechanism by which the altered expression of miR-378 affects tumor development and progression has not been elucidated and its involvement in CRC has not been addressed in detail. [score:4]
Recently, miR-378 expression was shown to be deregulated in oral carcinoma and renal cell carcinoma [11, 12]. [score:4]
Our data implicated the potential application of miR-378 as a tumor suppressor in CRC therapy and also as a tumor marker for predicting prognosis. [score:3]
Correlation between miR-378 expression and clinical features and prognosis of CRC patients. [score:3]
Kaplan–Meier and Cox proportional regression analyses were utilized to determine the association of miR-378 expression with survival of patients. [score:3]
Figure 1 The relative expression levels of miR-378 in CRC tissues and cell lines. [score:3]
The bars in the figure indicate the means of the relative expressions of miR-378. [score:3]
After 5 weeks, miR-378 over -expressing tumors were significantly smaller than those of mice transfected with scramble control (Figure  4A). [score:3]
Furthermore, overexpression of miR-378 significantly reduced xenograft tumor volume (Figure  4B) and tumor weight (Figure  4C). [score:3]
On the contrary, when transfected with miR-378 inhibitors, SW620 cells exhibited stimulated proliferation as well as invasive capabilities. [score:3]
This study first showed that miR-378 may function as a tumor suppressor in CRC. [score:3]
Kaplan–Meier survival analysis showed that low miR-378 expression correlated with shorter overall survival (Figure  2, P = 0.004). [score:3]
Aberrant expression of miR-378 has been found in some types of cancer. [score:3]
Therefore, in this study, we confirmed the expression of miR-378 in fresh CRC tissue specimens and CRC cell lines by using qRT-PCR. [score:3]
Secondly, over -expression of miR-378 significantly reduces the activity of a luciferase reporter containing the 3′UTR sequence of vimentin. [score:3]
In addition, vimentin has been confirmed as a target gene of miR-378 in glioblastoma Cells [30]. [score:3]
The bioinformatics analysis indicates that vimentin may be the potential target for miR-378. [score:3]
All of the algorithms indicated that vimentin was a theoretical target of miR-378 (Figure  5A). [score:3]
Figure 2 Kaplan–Meier survival curves of patients with colorectal cancer based on miR-378 expression status. [score:3]
When combined with bioinformatic analysis, we concluded vimentin was a target gene of miR-378 in CRC. [score:3]
We performed quantitative PCR analysis to detect the expression level of miR-378 in CRC tissues and cell lines. [score:3]
The miR-378 expression in CRC tissues and cell lines. [score:3]
The expression of miR-378 was then assessed in four CRC cell lines (SW620, SW480, HT29 and HCT116) and the normal colon epithelium cell line CCD-18Co. [score:3]
The pre-miR miRNA-378(Pre-miR-378), pre-miR negative control (Pre- miR-nc), anti-miR negative control (anti-miR-nc) and anti-miR-378 inhibitor (anti-miR-378) were purchased from Ambion (Austin, TX,USA). [score:3]
Therefore, the function of miR-378 is complicated because it can be oncogenic or a tumor suppressor in different types of cancers. [score:3]
It suggested a potential regulation of vimentin by miR-378. [score:2]
To examine the role of miR-378 in CRC tumor development, we used a BALB/C nude xenograft mouse mo del in which mice were transplanted with pre-miR-378 and pre-miR-nc transfected cells. [score:2]
MiR-378 inhibits tumor growth in vivo. [score:2]
In summary, our present study showed that miR-378 was down- regulated in CRC tissues and cell lines. [score:2]
Correspondingly, we also generated a mutant reporter vector which contains the vimentin 3′-UTR with a mutation at the putative miR-378 binding site (Figure  5A). [score:2]
Univariate proportional hazard mo del revealed a statistically significant correlation between overall survival and miR-378 level, tumour size, local invasion, lymph node metastasis, and TNM stage (Table 2). [score:1]
Our present results implicate the potential effects of miR-378 on prognosis and treatment of CRC cancer. [score:1]
Since TNM stage is determined by the local invasion and lymph node metastasis, it was not further enrolled into the multivariate analysis in this study, and the results of the multivariate analysis demonstrated that miR-378 (P = 0.037) and lymph node metastasis (P = 0.001) were independent prognostic factors for overall survival (Table  2). [score:1]
MTT and invasion assays were used to determine the role of miR-378 in regulation of CRC cancer cell growth and invasion, respectively. [score:1]
Figure 3 Effects of miR-378 on proliferation and invasion of SW620 cell line. [score:1]
The involvement of miR-378 in the tumorigenesis and metastasis of glioblastoma, non-small cell lung cancer, breast cancer and gastric cancer has also been reported [13- 16]. [score:1]
Pre-miR-378 or pre-miR-nc stable transfection SW620 cells suspensions (1 × 10 [6] cells/ml) in 200 μl serum-free medium were subcutaneously injected into the flanks of nude mice, respectively. [score:1]
After that, we assessed the clinical significance of miR-378 in colorectal cancer, and to investigate the effects of miR-378 on CRC cells growth and invasion and further discuss the mechanisms of action of miR-378 by identifying its potential target gene. [score:1]
To validate if miR-378 regulates CRC cell growth, we performed a proliferation assay by transfecting pre-miR-378 or pre-miR-nc into SW620 cells. [score:1]
It suggested a potential inverse relevance of miR-378 and vimentin in CRC. [score:1]
However, effects and potential mechanisms of miR-378 in colorectal cancer (CRC) have not been explored. [score:1]
To evaluate the correlation between miR-378 expression and clinicopathological characteristics, the 84 patients with CRC cancer were classified into two groups according to the median expression (2.77) of miR-378. [score:1]
Effect of miR-378 on CRC cell growth and invasion in vitro. [score:1]
These results indicated that miR-378 may be involved in the progression of CRC and predict overall survival in CRC. [score:1]
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[35] Paradoxically, some researchers have found that miR-378 may suppress luteal cell apoptosis by targeting the interferon gamma receptor 1 gene, [36] and the overexpression of miR-378 attenuates I/R -induced cell apoptosis by inhibiting caspase-3 expression in cardiomyocytes. [score:11]
These results imply that the protective effects of miR-378 following intestinal ischemia are likely mediated by the inhibition of cell apoptosis via the translational repression of caspase-3. MiRNAs are known to be important mediators of gene regulation in response to cell-to-cell signaling and to act in the negative feedback of gene regulation, 16, 17 which affects several biological processes, such as development, [26] differentiation, [27] apoptosis 28, 29, 30 and oncogenesis. [score:8]
For example, a recent study demonstrated that the downregulation of miR-378 supports cell survival by targeting the insulin-like growth factor receptor in cardiomyocytes and acts as a negative regulator. [score:7]
To assess the function of elevated levels of miR-378 in IEC-6 cells, pre-miR-378 (mimic) and miR-378 inhibitor were transfected for miR-378 overexpression and inhibition, respectively. [score:7]
Lee et al. [46] found that miR-378 transfection could enhance cell survival and could reduce caspase-3 activity by inhibiting the expression of suppressor of fused and Fus-1. Caspase-3 is a well-established executor of apoptosis that acts by cleaving various substrate proteins and also amplifies the death signal from the plasma membrane by activating additional caspases. [score:7]
Further studies revealed that increased expression of miR-378 attenuated intestinal I/R injury by inhibiting intestinal mucosal cell apoptosis, which is associated with the regulatory effects of miR-378 on caspase-3 signaling. [score:6]
This study was the first to analyze miRNA expression profiles in the intestinal mucosa after intestinal I/R and to find that miR-378 is significantly downregulated during the process. [score:6]
Furthermore, pretreatment with the miR-378 inhibitor further increased the cleaved caspase-3 expression (Figures 4e and f). [score:5]
Second, overexpression of miR-378 reduced intestinal epithelial cell apoptosis in both in vivo and in vitro ischemic mo dels and attenuated cleaved caspase-3 expression. [score:5]
In this study, we found that intestinal I/R caused severe intestinal injury accompanied by a significant magnitude of miRNA expression, and overexpression of miR-378 decreased caspase-3 activation and reduced intestinal mucosa cell apoptosis/necrosis both in vivo and in vitro. [score:5]
As intestinal epithelial cell apoptosis has been known to contribute to intestinal I/R injury, and a reduction in intestinal mucosa apoptosis could reduce the intestinal injury induced by I/R, it can be concluded that the overexpression of miR-378 attenuated intestinal I/R injury by inhibiting intestinal epithelial cell apoptosis. [score:5]
In vitro overexpression of miR-378 improves IEC-6 cell survival after OGD/R challengeAs illustrated in Figure 4a, the transfection of the pre-miR-378 (mimic) or miR-378 inhibitor, but not their NCs, significantly increased or decreased the miR-378 levels in the normoxic cells. [score:5]
Among these differentially expressed miRNAs, let-7b, miR-26b, miR-182, miR-192, let-7d, miR-15b, miR-16, let-7a and miR-378, were confirmed by RT-qPCR to exhibit marked decreases in expression in the intestinal mucosa following intestinal I/R (Table 2). [score:5]
Our observation is consistent with recent reports that have demonstrated that miR-378 targets cleaved caspase-3. Wang et al. [45] reported that miR-378 inhibits cell growth and enhances L-OHP -induced apoptosis in human colorectal cancer. [score:5]
To generate miRNA-378 overexpression TG mice, the specific promoter and pronuclear injection were used to drive the expression of miR-378 in mice. [score:5]
To generate miRNA-378 -overexpressing TG mice, the specific promoter and pronuclear injection were used to drive the expression of miR-378 in founder mice. [score:5]
The protection rendered by miR-378 may represent a potential novel therapeutic target for the treatment of diseases related to intestinal I/R injury. [score:5]
MiR-378 is one of these markedly decreased miRNAs and was found to be the putative target mRNA linked to cell death based on the application of the TargetScan, miRanda, CLIP-Seq and miRDB prediction algorithms. [score:5]
[44] Although our study has identified a relationship between miR-378 and its target caspase-3 in the ischemic intestine using prediction algorithms (i. e., TargetScan, miRanda, CLIP-Seq and miRDB) and the dual-luciferase reporter assay, the protection afforded by the miR-378 mimetic is only partial, and therefore, other miRNAs and mRNAs might also have a role in the damage-sparing mechanism. [score:4]
These results indicated that miR-378 decreased the expression of caspase-3 through its direct binding with the caspase-3 3’-UTR. [score:4]
MiR-378 reduces caspase-3 expression in the intestine by targeting the 3’-UTR of caspase-3. Discussion. [score:4]
Identification of downregulated miR-378 in the intestines of mice following intestinal I/R. [score:4]
Consequently, miR-378 was found to exhibit a significant fold change (3.38-fold downregulation, validated by RT-qPCR) among the I/R -induced miRNAs (Table 2). [score:4]
RT-qPCR analysis revealed that miR-378 was successfully overexpressed in TG mice to a level of 3.39-fold that observed in WT mice (Figure 3a). [score:3]
Consistent with the flow cytometric analysis, miR-378 mimic transfection resulted in a significant downregulation of cleaved caspase-3 when compared with the OGD/R group. [score:3]
In vivo overexpression of miR-378 ameliorates the intestinal mucosal injury and cell apoptosis induced by intestinal I/RThe miR-378 level was detected by RT-qPCR to confirm the construction of the miR-378 transgenic (TG) mouse mo del. [score:3]
Furthermore, we demonstrated that the overexpression of miR-378 significantly ameliorated intestinal tissue damage in WT/TG mice and OGD-challenged IEC-6 cell injury. [score:3]
The level of miR-378 was detected in the third-generation mice by RT-qPCR, normalized to U6, and expressed as the fold change relative to the WT control. [score:3]
Caspase-3, a critical executor of apoptosis, is one of the predicted putative targets of miR-378 based on the prediction algorithms. [score:3]
In vitro overexpression of miR-378 improves IEC-6 cell survival after OGD/R challenge. [score:3]
As illustrated, the expression of miR-378 in the TG mouse was 3.39 times that in the WT mice (Figure 3a). [score:3]
Moreover, among the 40 predicted putative targets of miR-378, three are common to the above four algorithms, including MTSS1L, NEUROD1 and CASPASE-3 (Table 3). [score:3]
Moreover, miR-378 expression in the antagomir group was significantly lower than that in the injury group (Figure 2a). [score:3]
Consistent with the evidence of intestinal protection in vivo, our in vitro data demonstrated that the intestinal apoptotic/necrotic cells were also markedly reduced when pretransfected with miR-378 mimic in the OGD/R-challenged IEC-6 cells, whereas miR-378 inhibitor transfection aggravated the apoptotic and necrotic cells (Figure 4d). [score:3]
Expression of miR-378 was detected on the fourth day by RT-qPCR. [score:3]
In vivo overexpression of miR-378 ameliorates the intestinal mucosal injury and cell apoptosis induced by intestinal I/R. [score:3]
[38] Therefore, we first used agomiR-378 and antagomiR-378 and found that they significantly increased and decreased miR-378 expression in the intestinal mucosa, respectively (Figure 2a). [score:3]
As demonstrated, miR-378 overexpression in TG mice alleviated intestinal I/R injury (Figures 3b and f). [score:3]
These data indicate that increased expression of miR-378 exerts anti-apoptotic properties. [score:3]
Predicted targets of miR-378. [score:3]
Transfection with pre-miR-378 could significantly reduce, whereas the miR-378 inhibitor aggravated, the numbers of apoptotic and necrotic OGD/R cells (Figure 4d). [score:3]
Our results showed that, in miRNA-378 overexpressing TG mice, the addition of agomiR-378 and miR-378 mimic decreased caspase-3 cleavage. [score:3]
As illustrated in Figure 4a, the transfection of the pre-miR-378 (mimic) or miR-378 inhibitor, but not their NCs, significantly increased or decreased the miR-378 levels in the normoxic cells. [score:3]
MiRNA-378 -overexpressing TG (Cyagen Biosciences, Guangzhou, China) mice were produced by pronuclear injection. [score:2]
Moreover, pretreatment with the miR-378 inhibitor further exacerbated cell death when compared with the OGD/R group (Figure 4b). [score:2]
By contrast, the IEC-6 cell viability was further decreased compared with the OGD/R group following pretreatment with the miR-378 inhibitor (Figure 4b). [score:2]
Three days after injection of agomir-378, antagomir-378 or their negative control (NC), miR-378 expression was significantly preserved in the agomir group compared with the other ischemic insult groups. [score:2]
The co-transfection of 293 T cells with caspase-3-luc and a miR-378 mimic reduced the expression of luciferase by 46% compared with the results following NC caspase-3-luc/miR-378 mimic co-transfection (Figure 5b). [score:2]
[55] MiR-378 mimic and inhibitor NCs were also involved in this study. [score:2]
A dual-luciferase reporter assay was performed to validate caspase-3 as a putative target of miR-378. [score:2]
[37] Therefore, the role of miR-378 in the regulation of intestinal epithelial cell death remains an enigma. [score:2]
Previous studies have demonstrated the role of miR-378 in the regulation of cell apoptosis. [score:2]
MiR-378 is predicted to have many potential targets. [score:2]
293 T cells (5 × 10 [4]cells/well) were cultured in 48-well plates for 24 h and then transfected with PMIR-RB-REPORT-caspase-3-3’-UTR (1  μg/well) (RiboBio) and miR-378 mimic (100 nm per well) or a NC, separately. [score:1]
The miR-378 level was detected by RT-qPCR to confirm the construction of the miR-378 transgenic (TG) mouse mo del. [score:1]
[52] In vivo administration of agomiR-378 and antagomiR-378To investigate the effects of miRNA-378 following intestinal I/R injury, the chemically modified agomir and antagomir were used to increase or decrease miRNA expression in vivo. [score:1]
Taken together, our results highlight the crucial role of miR-378 in reducing the intestinal injury induced by I/R. [score:1]
One miR-378 -binding site was identified within the 3’-UTR of the caspase-3 mRNA (Figure 5a). [score:1]
[52] To investigate the effects of miRNA-378 following intestinal I/R injury, the chemically modified agomir and antagomir were used to increase or decrease miRNA expression in vivo. [score:1]
In this study, we found that the intestinal mucosal cell apoptotic index was reduced following pretreatment with miR-378 agomir, whereas miR-378 antagomir administration increased the apoptotic index. [score:1]
Briefly, we first acquired the genomic sequence of miR-378 from the Origene company (OriGene Technologies, Rockville, MD, USA) website, then intercepted Villin genes upstream of the transcription start 7-kb site and the first intron 5.5 kb of sequence based on previous studies. [score:1]
Mir-378 amplification: DsRed2-mir-378-F: 5′-GTTCCAGTAGCAGTTGTCAGCAGAAGCAGTG-3′, NotI-mir-378-R: 5′-AAGGAAAAAAGCGGCCGCCTGGGTTAGCCACCAAAGAC-3′, Vector of pStar-K for subsequent restructuring: pStar-K-F: 5′-ATTTCCCAGATGGGACTACGC-3′, pStar-K-R: 5′-GGCAATGGCAGAGTGAAGAG-3′. [score:1]
was used to further confirm whether miR-378 could affect 4 h OGD/4 h reoxygenation -induced IEC-6 cell apoptosis. [score:1]
However, whether miR-378 changes the mitochondrial function or ATP biogenesis remains to be determined in the future. [score:1]
[41] Consistent with evidence from the intestinal protection in vivo, our in vitro data revealed that IEC-6 cell viability was significantly preserved after transfection with the miR-378 mimic, whereas OGD/R challenge led to obvious cell death. [score:1]
MiR-378 agomir protects against ischemic intestinal injury and cell apoptosis in the wild-type (WT) mouse intestinal I/R mo del. [score:1]
[52] In vivo administration of agomiR-378 and antagomiR-378To investigate the effects of miRNA-378 following intestinal I/R injury, the chemically modified agomir and antagomir were used to increase or decrease miRNA expression in vivo. [score:1]
Second, because several miRNAs responded rapidly to intestinal I/R, this study only investigated the function of miR-378 in ischemic intestine; whether other differentially expressed miRNAs (miR-182, miR-192, let-7a, etc. ) [score:1]
Thus, we selected miR-378 for further functional studies. [score:1]
Therefore, it is necessary to evaluate the long-term and global consequences of miR-378 overexpression in adult mice. [score:1]
Obviously, the current results indicated that miR-378 may have a protective role in intestinal I/R -induced intestinal injury. [score:1]
By contrast, miR-378 antagomir pretreatment aggravated the intestinal tissue injury (Figures 2b and f). [score:1]
DsRed2 amplification: Downstream-DsRed2-F: 5′-GCCACCATGGATAGCACTGAGAACGTC-3′, DsRed2-mir-378-R: 5′-CACTGCTTCTGCTGACAACTGCTACTGGAACAGGTGGTGG-3′. [score:1]
Generation of a miR-378 TG mouse mo del. [score:1]
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Since the under-expressed genes are more likely to be the direct targets of miR-378, we then focused on the genes in Group I and Group III and defined the genes in these two groups as miR-378 directly targeted circadian oscillating genes, denoted as miR-378 circadian targets. [score:11]
In NIH-3T3 cells, Cdkn1a is also significantly under-expressed in miR-378 over -expression and up-regulated in miR-378 inhibition 32. [score:10]
BMAL1 ChIP-PCR analysis, analysis of mouse liver circadian miRNA-seq data, qPCR of mature miR-378-3p and miR-378-5p expression, circadian miRNA target identification, RNA-sequencing and data analysis, miR-378-3p targets in NIH-3T3 cell, mouse liver circadian database, comparison of the relative circadian amplitudes of nascent and mature transcripts, and regulation of circadian TFs are available in the Supplementary information. [score:8]
Comparing with miR-378 target genes identified by another genome-wide study of miR-378-3p in NIH-3T3 cells 32, we again found a significant overlap between their result and our under-expressed genes by miR-378 over -expression in mouse liver (Fig. 4b). [score:7]
The left figures show the expression patterns of nascent and mature transcripts and the right figures show the expression patterns upon miR-378 over -expression. [score:7]
In our study, two metabolic genes (Pdk4 and Por) showing robust circadian expression in mouse liver are under-expressed upon miR-378 over -expression. [score:7]
For the miR-378 circadian target genes that lack circadian transcriptional regulation, miR-378 alone can lead to their circadian expression by rhythmic post-transcriptional regulation. [score:7]
As the mature miRNA-378-3p and miRNA-378-5p still showed low amplitudes of circadian oscillation, the circadian expression of these targets may be driven by rhythmic post-transcriptional regulation through miRNA-378. [score:6]
For the rest of miR-378 circadian targets that do not show significant amplitude changes, it is still possible that they are strongly regulated by miR-378 in wild type mice so that miR-378 over -expression can not increase their amplitudes further. [score:6]
Furthermore, 833 genes showing significant difference in expression between CT10 and CT22 were affected by miR-378 over -expression (ANOVA p-value for treatment < 0.05 and ANOVA p-value for time < 0.05) (Fig. 4e). [score:5]
Supporting this mo del, we identified 79 miR-378 circadian targets that showed increased relative amplitudes upon miR-378 over -expression. [score:5]
Among these genes, the under-expressed genes in Ad-378 compared to Ad -null were over-represented by as much as eight-fold, consistent with the inhibitory role of miR-378 in gene regulation. [score:5]
We observed that both cyclin E1 (Ccne1) peaking around CT10, which is required for cell cycle G1/S transition and Cdkn1a peaking around CT22, which inhibits G1/S transition, are miR-378 circadian targets. [score:5]
Among the cell cycle genes targeted by miR-378, Ccne1 peaking around CT10 is required for cell cycle G1/S transition, while Cdkn1a, an inhibitor of G1/S transition, shows circadian peak around CT22 and has long been shown to be repressed by REV-ERBα 42. [score:5]
In human breast cancer cells, miR-378 induces metabolic shift by inhibiting the expression of two PGC1β partners, ERRγ and GABPA. [score:5]
cn/), we found a significant enrichment of the putative miR-378 targets in the under-expressed genes (Fisher’s exact test p-value = 1.43×10 [−12], odd ratio = 1.82). [score:5]
The expression of miR-378 shows circadian oscillation peaking at CT10 and is regulated by BMAL1/CLOCK. [score:4]
Namely, a significantly elevated proportion (14.2%) of the under-expressed genes are circadian oscillating in mouse liver as compared to only 10% of the un-affected genes upon miR-378 over -expression (Fig. 4c). [score:4]
Consistent with our result, Ma et al. showed that miR-378 promotes the migration and metastasis of liver cancer cells by down -regulating Fus expression 29. [score:4]
The same qPCR procedure was applied to validate the expression pattern of cell cycle genes upon miR-378 over -expression, and the primers for the cell cycle genes were listed in Supplementary Table S10. [score:4]
Second, we observed that the genes under rhythmic post-transcriptional regulation significantly enriched in miR-378 circadian targets. [score:4]
Five miR-378 circadian targets involved in cell cycle regulation (Ccne1, Runx3, Cdkn1a, Bbc3, and Bcl2) were selected to be validated by qPCR. [score:4]
We suggested that miRNA-378 might regulate different groups of target genes by cooperating with different circadian TFs (Fig. 5d). [score:4]
This suggests that these genes may be already under strong regulation by miR-378 such that the over -expression of miR-378 does not further increase their circadian amplitudes. [score:4]
We examined the expression changes of mature miR-378-3p and miR-378-5p in liver-specific Bmal1 c KO mice and wild-type mice by miRNA specific qPCR (materials and methods). [score:3]
We overlapped the miR-378 circadian targets in our study with Lück et al. ’s result. [score:3]
The efficiency of miR-378 over -expression in liver was about 50 folds as examined by miRNA specific qPCR (Supplementary Fig. S3). [score:3]
Therefore, circadian post-transcriptional regulation of Fus by miR-378 can further contribute to the circadian regulation of cell cycle. [score:3]
Ad -null) as two factors to identify the genes that are affected by miR-378 over -expression. [score:3]
Through both of our motifs, miR-378 can further fine-tune the circadian amplitudes of target genes by increasing their degradation rates. [score:3]
In particular, Cdkn1a showed more than four-fold relative amplitude increase upon miR-378 over -expression. [score:3]
Accession codes: RNA-seq data of miR-378 over -expression and liver-specific Bmal1 c KO were submitted to GEO under accession numbers GSE73308 and GSE73271. [score:3]
Genome-wide effects of miR-378 over -expression. [score:3]
Circadian oscillating genes are significantly affected by miR-378 over -expression. [score:3]
In the light of our result, there are two scenarios of how miR-378 could exert its impact on circadian expression. [score:3]
Consistent with the RNA-seq data, all of them showed significant changes upon miR-378 over -expression. [score:3]
To explore the circadian functions of miR-378, we injected adenovirus over -expressing both miR-378-3p and miR-378-5p into mice (termed Ad-378) while the control mice were injected with null virus (termed Ad -null, materials and methods). [score:3]
In mouse liver, it has been shown that miR-378 targets p110 α and controls glucose and lipid homeostasis by modulating hepatic insulin signaling 30. [score:3]
However we still identified 47 circadian oscillation genes peaking around CT10 (red dots in Fig. 5a) and 32 genes peaking around CT22 (blue dots in Fig. 5a) showing increased relative amplitudes upon miR-378 over -expression. [score:3]
5 × 10 [8] plaque-forming unit viruses were administered to four Ad-378 mice through tail vein injection for miR-378 over -expression. [score:3]
The liver samples of Ad-378 and Ad -null mice were collected at CT10 and CT22 corresponding to the expression peak and trough of miR-378 respectively. [score:3]
Ad -null, less than 0.05 as the cutoff, we obtained 3,718 genes affected by miR-378 over -expression (Fig. 4a). [score:3]
Transcriptome profile of miR-378 over -expression in mouse liver. [score:3]
The post-transcriptional regulation of these genes by miR-378 may play a predominant role in their circadian regulation. [score:3]
Comparing the relative amplitude defined as the log2-transformed fold changes between CT10 and CT22, i. e. log [2]FC(CT10/CT22), of Ad-378 and Ad -null, we observed that 80% of miR-378 circadian targets showed little or no differences in relative amplitudes (Fig. 5a), i. e. relative amplitude differences less than 0.5. [score:3]
Our findings may provide the explanation of the time-of-day dependent function of miR-378 in the regulation of cell cycle and metabolism. [score:2]
We have provided evidences for the role of miR-378 in circadian regulation. [score:2]
Therefore, miR-378 can influence the relative circadian amplitudes of cell cycle related genes by regulating their mRNA degradation rates. [score:2]
It suggests that miR-378 may have dual roles in the circadian regulation of cell cycle progression. [score:2]
miR-378 in circadian gene regulation. [score:2]
miR-378 is involved in circadian gene regulation. [score:2]
In the first motif, which is a feed-forward loop (FFL), miR-378 cooperated with BMAL1/CLOCK to regulate the genes including Gadd45a and Por with the circadian peak around CT10. [score:2]
These observations suggested that miR-378 is under the regulation of BMAL1/CLOCK at both primary and mature levels. [score:2]
In the second motif, miR-378 cooperated with REV-ERBα/β to regulate the genes including Cdkn1a and Bcl2 with circadian peaks around CT22. [score:2]
We found that the weak oscillations of miR-378-3p as well as miR-378-5p were abolished in liver-specific Bmal1 c KO mice (Fig. 3b). [score:1]
Our functional annotation has pointed to the cross talk between circadian rhythm and cell cycle through miR-378. [score:1]
Basically, DNA fragments encoding miR-378 were introduced into pENTR/U6 vector under the control of the human U6 promoter. [score:1]
We found that four miRNAs (miR-24-3p, miR-101a-3p, miR-378-3p and miR-122-3p) showed significant circadian oscillations at mature levels with peak times close to those of their primary transcripts. [score:1]
This is also consistent with the known function of miR-378 in cell cycle. [score:1]
For all of them we can find the putative miR-378 binding sites on their 3′UTRs using Miranda algorithm (Fig. S5). [score:1]
In addition, miR-378 has been reported to be involved in metabolic process. [score:1]
As such, we constructed a gene network involving miR-378 and circadian TFs (Fig. S7). [score:1]
Our BMAL1 ChIP-PCR experiment in mouse livers validated the physical binding of BMAL1 on the promoters of three selected circadian miRNA primary transcripts, pri-mir-23b~27b~24-1, pri-mir-101a, and pri-mir-378 (Fig. 2b). [score:1]
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[+] score: 210
Upregulation of miR-378 in A549/cDDP cells significantly down-regulates sCLU expression, and enhances the sensitivity of A549/cDDP cells to cDDP. [score:9]
In conclusion, we report altered expression of miR-378 in human lung adenocarcinoma cell lines with varying sensitivities to cDDP, and have shown that miR-378 can restore cDDP chemosensitivity in the human lung adenocarcinoma cells by targeting sCLU and downregulating Bcl-2, pCas-3, pErk1/2 and pAkt (Fig. 7). [score:8]
The upper panel showed the growth curves, and the lower panel showed the representative picture of tumors with miR-378 overexpression (right) and Mock (left); (B) showed miR-378 inhibited sCLU expression. [score:7]
showed that either downregulation of sCLU or overexpression of miR-378 increased cell apoptosis in A549/cDDP cells and Anip973/cDDP. [score:6]
It has been shown previously that selective regulation of microRNA activity can improve responsiveness to chemotherapy 20. miR-378 expression is found in a number of cancer cell lines 21 22, and is related to the expression of vascular endothelial growth factor 23 24. [score:6]
Fei et al. reported that miR-378 suppress HBV-related hepatocellular carcinoma tumor growth by directly targeting the insulin-like growth factor 1 receptor 26. [score:6]
In addition, overexpression of miR-378 in A549 cells or Anip973 (both with low CLU expression 8) also had no effect on the sensitivity of the cells. [score:5]
Furthermore, overexpression of miR-378 can reduce the sCLU level (Fig. 3A), sensitize A549/cDDP and Anip973/cDDP cells to cDDP (Fig. 2A, supplement Figures 1B and 4A), and inhibit the tumor growth in nude mice mo del (Fig. 5A). [score:5]
Forced expression of sCLU eliminated most of the gains in the sensitivity to cDDP in miR-378 -overexpressing cells (Fig. 4A), and reversed the decrease of Bcl-2, pCas-3, pErk1/2 and pAkt (Fig. 4B). [score:5]
Taken together, these results suggest that miR-378 suppresses sCLU gene expression through the 3′-UTR binding and silencing of sCLU mRNA. [score:5]
miR-378 inhibited tumor growth and sCLU expression in Nude mouse tumor xenograft mo del. [score:5]
Wang et al. found that miR-378 inhibited cell growth and enhanced L-OHP -induced apoptosis in human colorectal cancer by targeting CDC40 25. [score:5]
miR-378 inhibited tumor growth and sCLU expression in a nude mouse tumor xenograft mo del. [score:5]
In this study, we identified sCLU as a novel target of miR-378; we demonstrated that miR-378 overexpression could decrease sCLU, enhance cell apoptosis, and sensitize lung adenocarcinoma to cDDP both in vitro and in vivo. [score:5]
We found that miR-378 is partially complementary to the 3′ untranslated region (UTR) of the CLU mRNAs using Bioinformatics (TargetScan) (Fig. 1A), and miR-378 can affect the luciferase activity due to canonical binding to sCLU 3′-UTR (Fig. 1B). [score:5]
demonstrated that sCLU was significantly down-regulated in the A549/cDDP-miR-378 cells (P < 0.05) (Fig. 5B). [score:4]
The result showed that upregulation of miR-378 led to a significant decrease of sCLU protein in A549/cDDP cells (Fig. 3A). [score:4]
miR-378 directly targets sCLU. [score:4]
miR-378 targets sCLU and regulated its cell signal. [score:4]
Collectively, these data strongly suggest that miR-378 regulate chemo-resistance to cDDP by targeting sCLU. [score:4]
miR-378 directly Targets sCLU. [score:4]
The results showed that upregulation of miR-378 led to a significantly increased sensitivity to cDDP in A549/cDDP cells (Fig. 3B). [score:4]
The results showed that up-regulation of miR-378 significantly decreased the relative luciferase activity of wild type but had no effect on the mutant 3′UTR of sCLU (Fig. 1B). [score:4]
Similar results also could be seen in Anip973/cDDP, another cell line with high CLU expression 8. After sCLU knockdown, miR-378 transfection had no effect on the sensitivity of the cells (Supplementary Figure 1B). [score:4]
The results showed that overexpression of miR-378, or knockdown of sCLU, both sensitized the cells to cDDP (Fig. 2A). [score:4]
As two sets of observations showed that miR-378 is important in chemoresistance to cDDP 15 16, and as we found that miR-378 was identified as one of the miRNA that target sCLU, we focused our research on miR-378. [score:3]
The tumor growth curve analysis showed that miR-378 significantly inhibited the tumor growth in 18 days after the injection of cells (p < 0.05) (Fig. 5A). [score:3]
sCLU is involved in miR-378 -induced cisplatin resistance in vitroTo test whether sCLU is a target of miR-378, was used to check the effect of miR-378 transfection on sCLU in the A549/cDDP cell line. [score:3]
Interestingly, previous studies have indicated that miR-378 transfection enhanced cell survival, tumor growth, and angiogenesis in NSCLC cells, but target genes were not identified 23 24. [score:3]
Correlation analysis showed that miR-378 was negatively correlated with sCLU expression level (r = −0.538). [score:3]
As shown in Fig. 1A, the sequence of miR-378 was partially complementary to the 3′ untranslated region (UTR) of the sCLU mRNAs (7 nucleotides completely match). [score:3]
Moreover, our data are also corroborated by the observations in human tumor tissues obtained from patients who showed sensitivity or insensitivity to cDDP, and we found an inverse correlation between miR-378 and sCLU expression levels in tumor tissues samples. [score:3]
C. Correlation analysis shows that miR-378 negatively correlates with the sCLU mRNA expression level, r = −0.538. [score:3]
org) to search the miRNAs that may target sCLU, which revealed many candidates (including miR-378). [score:3]
This data is corroborated by the expression of miR-378 and sCLU in A549 vs A549/cDDP (Fig. 1C,D) and Anip973 vs Anip973/cDDP 8 (supplementary Figure 1A). [score:3]
Therefore, targeting this miR-378-sCLU interaction may be a potential strategy for reversing cDDP chemoresistance in human lung adenocarcinoma. [score:3]
Based on the patients’ response to chemotherapy, they were divided into “sensitive” and “insensitive” groups, and the miR-378 levels and sCLU expression levels of each sample were analyzed. [score:3]
miR-378 transfection sensitized these cells to cDDP only after sCLU overexpression (supplementary Figure 2). [score:3]
With this in mind, the effect of miR-378 was determined by the function of target genes in the current study. [score:3]
To test whether sCLU is a target of miR-378, was used to check the effect of miR-378 transfection on sCLU in the A549/cDDP cell line. [score:3]
How to cite this article: Chen, X. et al. miRNA-378 reverses chemoresistance to cisplatin in lung adenocarcinoma cells by targeting secreted clusterin. [score:3]
To investigate how miR-378 overexpression affected sCLU expression and tumor growth, agomir-378 cells and cells with agomir-NC(Mock) were injected into the flank of nude mice. [score:3]
A mechanistic mo del of regulation of lung adenocarcinoma’s sensitivity to cDDP via miR-378 and sCLU. [score:2]
To our knowledge, our study is the first to demonstrate the association of miR-378 with the development of cDDP chemoresistance in human lung adenocarcinoma. [score:2]
Next, we compared the expression of miR-378 and sCLU in the cisplatin-resistant A549 cell line (A549/cDDP) with its parental A549 cell line. [score:2]
The expression level of miR-378 was detected with gene-specific primers as described 38. [score:2]
On the contrary, after sCLU knockdown, transfection of miR-378 did not change the apoptotic rate (Fig. 2B,C, and supplementary Figure 3). [score:2]
To verify that miR-378 targets sCLU, we cloned a fragment of CLU 3′UTR containing the putative miR-378 binding site, or its mutated one, into a luciferase reporter vector, and performed dual luciferase assays in 293T cells. [score:2]
We found that miR-378 expression level was significantly lower in the “insensitive” group tissues (0.40 ± 0.02) compared to the “sensitive” group (0.51 ± 0.03) (P < 0.05) (Fig. 6A). [score:2]
We transfected A549/cDDP cells with the miR-378 mimics(miR-378), and performed. [score:1]
sCLU is involved in miR-378 -induced cisplatin resistance in vitro. [score:1]
These results showed that miR-378’s effect on the sensitivity of the cells to cDDP or apoptosis depended on the presence of higher levels of sCLU, so it strongly indicated that miR-378 affected sensitivity of the cell and apoptosis through sCLU. [score:1]
miR-378 and sCLU affects A549/cDDP cell’s sensitivity to cDDP and apoptosis in cells. [score:1]
miR-378 increases sensitivity of A549/cDDP to cDDP and apoptosis through sCLU. [score:1]
Thus, we clearly established an inverse relationship between miR-378 and sCLU. [score:1]
The lower panel is the miR-378 sequence containing the putative sCLU binding site and its mutant sequence. [score:1]
After 8 days, Agomir-miR-378 or agomir-NC (RiboBio Co. [score:1]
To investigate the association between miR-378 and sCLU expression, 33 tumor tissue samples were obtained from patients with advanced lung adenocarcinoma. [score:1]
sCLU is involved in miR-378 -induced cisplatin resistance. [score:1]
We went further to test miR-378’s effect on apoptosis. [score:1]
To test miR-378’s effect on A549/cDDP’s sensitivity to cDDP, was performed. [score:1]
miR-378 and sCLU correlated with sensitivity to cDDP in lung adenocarcinoma tissues. [score:1]
miR-378 and sCLU are correlated with sensitivity to cDDP in lung adenocarcinoma tissues. [score:1]
To further examine whether sCLU is involved in miR-378 induced chemoresistance, we performed gain-of-function and loss-of-function analysis. [score:1]
Also, miR-378 is shown to be important in chemoresistance to cDDP, but no detailed mechanism is reported 15 16. [score:1]
miR-378 mimics, sCLU siRNA, sCLU(plasmid) or their controls were purchased from Sigma. [score:1]
HEK293T cells were seeded in a 24-well plate and transfected with 20 μM of either miR-378 mimics or miR-NC vectors, and 50 ng of psicheck-2 vectors. [score:1]
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[+] score: 186
In addition, protein expression of caspase-3 is significantly downregulated by miR-378 overexpression in the OGD -treated N2A cells. [score:8]
Overexpression of miR-378 could protect the neural cells against OGD or MCAO induced ischemic injury by targeting the apoptosis executioner caspase-3. In accordance with the changes of miR-378 in the peri-infarct region of MCAO mice [15], we examined the miR-378 expression in N2A cells during reoxygenation after 3 h OGD exposure. [score:7]
To further analyze the contribution of miR-378 targeting caspase-3 to the biological function of miR-378 in OGD -induced N2A cell injury, we performed siRNA -mediated inhibition of caspase-3 protein expression. [score:7]
Ma T. Jiang H. Gao Y. Zhao Y. Dai L. Xiong Q. Xu Y. Zhao Z. Zhang J. Microarray analysis of differentially expressed microRNAs in non-regressed and regressed bovine corpus luteum tissue; microRNA-378 may suppress luteal cell apoptosis by targeting the interferon γ receptor 1 gene J. Appl. [score:7]
Extensive evidence showed that miR-378 attenuated ischemic injury in cardiomyocytes by inhibiting caspase-3 expression, representing a potential novel treatment for apoptosis and ischemic heart disease [16]. [score:7]
Fang J. Song X. W. Tian J. Chen H. Y. Li D. F. Wang J. F. Ren A. J. Yuan W. J. Lin L. Overexpression of microRNA-378 attenuates ischemia -induced apoptosis by inhibiting caspase-3 expression in cardiac myocytes Apoptosis Int. [score:7]
Among the aberrantly expressed miRNAs, the downregulation of miR-378 in the peri-infarct region of middle cerebral artery occluded (MCAO) mice can be reversed by HPC pretreatment. [score:6]
As described by the previous report, miR-378 could inhibit caspase-3 protein expression and attenuated ischemic injury in cardiomyocytes [16]. [score:5]
Overexpression of miR-378 substantially suppressed the OGD -induced N2A cell death, whereas transfection of anti-miR-378 aggravated the cell death. [score:5]
In addition, pri-miR-378 effectively decreased the expression of caspase-3, whereas anti-miR-378 increased the expression of caspase-3 in mouse N2A cells exposed to 3 h OGD/24 h reoxygenation (Figure 3C,D, p < 0.05, n = 3 per group). [score:5]
In the present study, we used TargetScan to identify caspase-3 as the target gene of miR-378. [score:5]
Taken together, these results suggest that miR-378 directly regulated caspase-3 expression, which might be involved in the neuroprotection of miR-378. [score:5]
These data indicated that miR-378 directly regulated caspase-3 expression by binding to the 3′-UTR of Caspase-3 mRNA. [score:5]
Overexpression of miR-378 substantially suppressed the cell death, whereas transfection of anti-miR-378 aggravated the N2A cell death induced by 3 h OGD/24 h reoxygenation (Figure 1C–F, p < 0.05, n = 6 per group). [score:5]
In bovine corpus luteum tissue, miR-378 may suppress luteal cell apoptosis by targeting the interferon gamma receptor 1 gene [29]. [score:5]
Effect of miR-378 on the mRNA and Protein Expression Levels of Its Target Gene Caspase-3. 2.3. [score:5]
Western blot analysis showed that miR-378 agomir but not its negative control could downregulate caspase-3 protein level and cleaved-caspase-3 ratio in cerebral ischemic cortex of mice after 1 h MCAO/24 h reperfusion (Figure 4A–C p < 0.05, n = 4 per group). [score:4]
In the present study, we found that miR-378 was downregulated during reoxygenation in OGD -induced N2A cell ischemic mo del, which is consistent with the changes in the peri-infarct region of MCAO mice found by large-scale microarray screening in our previous report. [score:4]
Moreover, the luciferase reporter gene assay indicated that miR-378 targeted the 3′-UTR region of caspase-3 to decrease the protein level of the target gene. [score:4]
Lee D. Y. Deng Z. Wang C. H. Yang B. B. MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting sufu and FUS-1 expression Proc. [score:4]
In conclusion, we reported for the first time that the protective role of miR-378 in N2A cells after OGD in vitro and mouse brain following the MCAO -induced ischemic stroke in vivo through downregulating caspase-3 protein levels. [score:4]
We found that, among the significantly changed miRNAs, the reduced expression of miR-378 in the peri-infarct region of MCAO mice could be reversed by HPC pretreatment, indicating that miR-378 might be a key molecule in the development of neuroprotection. [score:4]
We found that the expression of miR-378 significantly decreased upon OGD treatment. [score:3]
However, other possible targets of miR-378 and the upstream regulation of miR-378 by transcriptional factors must also be investigated to fully understand the neuroprotective effect of miR-378 in the development of ischemic stroke. [score:3]
In accordance with the changes of miR-378 in the peri-infarct region of MCAO mice [15], we examined the miR-378 expression in N2A cells during reoxygenation after 3 h OGD exposure. [score:3]
To examine whether caspase-3 is responsible for OGD -induced N2A cell apoptosis, we analyzed the possibility of caspase-3 being a putative target of miR-378 by bioinformatics algorithms. [score:3]
This research points out a novel mechanism for the miR-378 induced neuroprotection by targeting caspase-3, which may become a potential therapeutic option for ischemic stroke. [score:3]
Experimentally, the expression of caspase-3 gradually increased at different reoxygenation times after OGD treatment, which is converse with the changes of miR-378 level. [score:3]
Then we examined the effect of miR-378 overexpression on MCAO -induced infarction and neural cell loss by TTC and Nissl staining, respectively. [score:3]
Huang Y. Liu X. Wang Y. MicroRNA-378 regulates neural stem cell proliferation and differentiation in vitro by modulating tailless expression Biochem. [score:3]
It is shown that expression of miR-378 can enhance cell survival, reduce caspase-3 activity, and promote tumor growth and angiogenesis [28]. [score:3]
Effect of miR-378 Overexpression on Transient Focal Cerebral Ischemic Injury of Mice. [score:3]
The results showed that miR-378 expression level decreased gradually and reached the platform at 24 h reoxygenation compared with the normoxic control (Figure 1A, p < 0.05, n = 5 per group). [score:2]
Most importantly, we found that miR-378 could induce neuroprotection through negatively regulating caspase-3 associated apoptosis. [score:2]
Caspase-3 Knockdown Blocked Anti-miR-378-Mediated Neuronal Injury in N2A Cells. [score:2]
To verify whether miR-378 can directly bind the 3′-UTR of Caspase-3 mRNA, we cloned a luciferase reporter encoding Caspase-3 3′-UTR, which contains the putative miR-378 binding sequences. [score:2]
In addition, caspase-3 knockdown could reverse anti-miR-378 mediated neural injury. [score:2]
Nagalingam R. S. Sundaresan N. R. Noor M. Gupta M. P. Solaro R. J. Gupta M. Deficiency of cardiomyocyte-specific microRNA-378 contributes to the development of cardiac fibrosis involving a transforming growth factor β (TGFΒ1) -dependent paracrine mechanism J. Biol. [score:2]
To further evaluate the biological role of miR-378 in cerebral ischemic injury in vivo, we employed a micro infusion pump to continuously deliver miR-378 agomir into the lateral ventricle to increase miR-378 expression. [score:1]
We found that there were potential binding sites between mmu-miR-378 and the 3′-UTR of Caspase-3 mRNA. [score:1]
Consequently, miR-378 agomir effectively attenuated infarction size (Figure 4D) and neuronal cell loss (Figure 4E–G, p < 0.05, n = 4 per group) in ischemic brain of MCAO mice. [score:1]
MTT results showed that caspase-3 siRNA had the ability to block anti-miR-378 -mediated neuronal injury induced by OGD treatment (Figure 5C, p < 0.05, n = 6 per group). [score:1]
The intracerebroventricular infusion of miR-378 agomir and its negative control was performed two days before MCAO as described [32, 33]. [score:1]
Recently, the potential role of miR-378 in cardiac remo deling [26], neural stem cell proliferation [27], and the progression of various carcinoma had been discovered. [score:1]
To determine the role of miR-378 in OGD -induced cell injury, we used pri-miR-378 and anti-miR-378 to alter miR-378 levels in cultured N2A cells. [score:1]
The following day, cells were co -transfected with 100 ng pmiR-RB-REPORT™ vector, including the 3′-UTR of Caspase-3 (with either wild-type or mutant miR-378 binding sites), and 100 ng pri-miR-378 or anti-miR-378 by using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA). [score:1]
A 668-bp segment from the 3′-UTR of the Caspase-3 gene containing miR-378 binding sites was amplified by PCR from 3T3 cell genomic DNA, and then cloned into the pmiR-RB-REPORT™ vector (Guangzhou RiboBio Co. [score:1]
Effect of miR-378 on OGD-Induced Ischemic Injury in N2A Cells. [score:1]
We also noticed that miR-378 could attenuate apoptosis examined by TUNEL and cleaved-caspase-3 staining. [score:1]
As shown in Figure 3E, the pri-miR-378 significantly decreased luciferase activity of the reporter vector containing 3′-UTR of Caspase-3 mRNA, but had no effect on the mutated reporter vector (p < 0.05, n = 6 per group). [score:1]
In specific experiments, mouse N2A cells were plated in 96-well or six-well plates and transfected with miR precursor (pri-miR-378), miR-378 antisence (anti-miR-378), and their negative controls (JIKAI, Shanghai, China) at a final concentration of 30 nM, or Caspase-3 and its negative control siRNAs (Gene Pharma, Shanghai, China) at a final concentration of 20 µM by using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s instructions. [score:1]
We then co -transfected these luciferase reporter vectors with pri-miR-378, pri-miR-378 ctrl, anti-miR-378, anti-miR-378 ctrl respectively into N2A cells. [score:1]
The results confirmed that transfection of pri-miR-378 attenuated 3 h OGD/24 h reoxygenation induced cell apoptosis, while anti-miR-378 aggravated 3 h OGD/24 h reoxygenation induced cell apoptosis (Figure 2C). [score:1]
However, until now, no evidence was known about the functional significance of miR-378 in cerebral ischemic injuries. [score:1]
Continuous infusion of mouse mmu-miR-378 (13314114400) agomir and its negative control (5 pmol/µL, 1 µL/h, Ribobio, Guangzhou, China) was conducted through a infusion cannula, which was stereotaxically implanted into the left lateral ventricle of the brain (Bregma: −2.2 mm, dorsoventral: 3 mm, lateral: 1 mm). [score:1]
However, pri-miR-378 and anti-miR-378 had no effect on Caspase-3 mRNA levels (Figure 3F, p < 0.05, n = 5 per group). [score:1]
Continuous delivery of the miR-378 agomir effectively attenuated MCAO -induced apoptosis, cerebral infarction, and neural cell loss. [score:1]
The above results indicated that miR-378 can exert neuroprotective effect partially by reducing caspase-3 associated cell apoptosis. [score:1]
This study is designed to further elucidate the role of miR-378 in the N2A cell ischemic mo del in vitro and the mouse focal ischemic stroke mo del in vivo. [score:1]
We also generated a mutant 3′-UTR of the Caspase-3 gene with substitution of 6 bp from seed region of the predicted mmu-miR-378 binding site. [score:1]
The present study showed that miR-378 level significantly decreased in N2A cells after OGD treatment. [score:1]
To our knowledge, this is the first report described the involvement of miR-378 in the in vitro and in vivo cerebral ischemic mo dels. [score:1]
Transfection of pri-miR-378 could significantly attenuate, while anti-miR-378 enhanced the number of TUNEL -positive cells. [score:1]
As shown in Figure 1B, transfection of pri-miR-378 or anti-miR-378, but not their negative controls, significantly increased or decreased miR-378 levels in normoxia and 3 h OGD followed by 24 h reoxygenation (p < 0.05, n = 5 per group). [score:1]
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[+] score: 73
To validate the data of the miRNA array, we conducted real-time quantitative reverse transcriptional polymerase chain reaction (qRT-PCR) for the expression of six upregulated miRNAs (mmu-miR-574-5p, mmu-miR-466i, mmu-miR-342-3p, mmu-let-7i, mmu-miR-34a and mmu-miR-188-5p) and five downregulated miRNAs (mmu-miR-378a-3p, mmu-miR-202, mmu-miR-378b, mmu-miR-378d and mmu-miR-212-3p) in liver tissues from the CCl [4] group (n = 5) and the control group (n = 4). [score:9]
Two Hh-activator genes, bmp4 and gli3, targeted by miR-378, were upregulated as miR-378 was downregulated in the fibrotic liver (Table 1 and Figure 6). [score:9]
On the other hand, the expression of Ihh, Wnt10b and Wnt11 was elevated with the increase of their regulatory miRNAs, miR-34a, miR-342-3p and miR-188-5p, respectively, and the level of Wnt6 was reduced with the decrease of its regulator miRNA, miR-378, in the CCl [4] group, implying that other regulatory factors might be additionally involved in the expression of these genes. [score:8]
Interestingly, five miRNAs, including three upregulated miRNAs (let-7i, miR-188-5p and miR-342-3p) and two downregulated miRNAs (miR-202-3p and miR-378), were related to 5830404H04Rik, a C2 calcium -dependent domain containing 2 (C2cd2). [score:7]
Among these 12 miRNAs, seven miRNAs, including mmu-miR-574-5p, mmu-miR-466i-5p, mmu-miR-342-3p, mmu-let7i-5p, mmu-miR-34a-5p, mmu-miR-188-5p and mmu-miR-5119, were upregulated, whereas five miRNAs, including mmu-miR-378a-3p, mmu-miR-202-3p, mmu-miR-378b, mmu-miR-378d and mmu-miR-212-3p, were downregulated in CCl [4] compared to the control group (Table 1). [score:6]
Among the downregulated miRNAs, the expression of miR-378 was validated in both the fibrotic livers of CCl [4] -treated mice and in the activated HSCs in our previous study [17]. [score:6]
In addition, the expression of w nt6 targeted by miR-378 decreased, despite the reduction of miR-378 in CCl [4] -treated liver. [score:5]
This reduced expression of miR-378 and induced expression of miR-34a-5p were also shown in the fibrotic liver of dimethylnitrosamine (DMN) -treated rats [64] and methionine/choline -deficient (MCD)-dieted mice [65]. [score:5]
Hyun J. Wang S. Kim J. Rao K. M. Park S. Y. Chung I. Ha C. -S. Kim S. -W. Yun Y. H. Jung Y. MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing GLI3 expression Nat. [score:4]
As described above, up- or downregulation of miR-378, miR-34a-5p and miR-202 was reported by other independent studies [64, 65, 66]. [score:4]
We demonstrated that miR-378 promoted the inactivation of HSCs by targeting Gli3, a transcriptional factor of Hh signaling. [score:3]
Prkaa2, one of the core target genes (Figure 3B) related to miR-378, miR-342-3p, miR-188-5p and let-7i, seems to be involved in the FoxO signaling pathway, mTOR signaling pathway, PI3K-Akt signaling pathway, AMPK signaling pathway, insulin signaling pathway and the adipocytokine signaling pathway. [score:3]
Because the reduced expression of miR-378a-3p, miR-378b and miR-378d in the fibrotic liver was demonstrated in the previous studies [17], duplicated results were not shown in the present study. [score:3]
Because miR-378a-3p, miR-378b and miR-378d were integrated into one miR-378 family in this analysis, three individual miRNA members were counted as one miRNA. [score:1]
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[+] score: 62
Furthermore, miR-145, miR-192, and miR-378 also showed inhibitory role in the expression of B7-DC, CTLA4 and PD-1. Taken together, our present study provides the first evidence that under-regulated miRNAs play significant roles in inhibiting translation of B7 co -inhibitory molecules, especially miR-143 in B7-H3 and B7-H4. [score:12]
We found that TGF-β1 upregulated the expression of miR-155, while downregulating the expression of miR-143, miR-145, miR-192, and miR-378 (Figure 4A). [score:11]
In addition, our results showed that miR-145, miR-192, and miR-378 suppressed the expression of co -inhibitory molecules B7-H3, B7-DC, CTLA4, and/or PD-1 (Supplementary Figure S3). [score:7]
MiR-143 inhibited the growth of CRC cells in vitro and in vivoGiven the important role of down-regulated miRNAs in cancer immune escaping, we assessed the impact of miR-143, miR-145, miR-192, and miR-378 on the growth of HCT-116 cancer cells. [score:6]
Interestingly, we found that the expression of miR-155 was inversely proportional to those of miR-143, miR-145, miR-192, and miR-378 in normal tissues (Figure 3D and 3E; Supplementary Table S3), conversely to the expression in adenoma and carcinoma tissues (Figure 3F and 3G). [score:5]
Down-regulation of miR-143, miR-145, miR-192, and miR-378 has also been well documented in many types of human tumors including colorectal cancer [38– 40]. [score:4]
was used to determine the effect of the down-regulated miRNAs, including miR-143, miR-145, miR-192, and miR-378, on the proliferation of HCT-116 cells. [score:4]
Given the important role of down-regulated miRNAs in cancer immune escaping, we assessed the impact of miR-143, miR-145, miR-192, and miR-378 on the growth of HCT-116 cancer cells. [score:4]
In the adenoma tissues, we found that the expression of miR-155, miR-143, miR-145, miR-192, and miR-378 were initially deregulated (Figure 3H). [score:4]
Figure 4(A) Impact of TGF-β1 on the expression of miR-143, miR-145, miR-155, miR-192, and miR-378 in HCT-116 cells. [score:3]
Figure 8(A) Impact of miR-143, miR-145, miR-192, and miR-378 mimics on the growth of HCT-116 cells in vitro. [score:1]
Figure 6(A) Predicted binding-sites of miR-143 and miR-378 in the 3′-UTRs of B7-H3 and B7-H4 genes. [score:1]
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[+] score: 58
Figure 7Activation of MET signaling in SMS-CTR ERMS cells induces proangiogenic effects in vitro by upregulation of miR-378, VEGF and MMP9, whereas MET silencing in RH30 ARMS exerts the opposite effects A. TPR-MET SMS-CTR cells conditioned media increase the amount of junctions, nodes and meshes formed by HUVEC cells in Matrigel angiogenesis assay in vitro, n = 4. B. Expression of VEGF, MMP9, miR-378a-5p and miR-378-3p is increased in SMS-CTR ERMS cells expressing TPR-MET and downregulated in shMET RH30 ARMS cells in vitro, qPCR, n = 2–4. [score:10]
A. TPR-MET SMS-CTR cells conditioned media increase the amount of junctions, nodes and meshes formed by HUVEC cells in Matrigel angiogenesis assay in vitro, n = 4. B. Expression of VEGF, MMP9, miR-378a-5p and miR-378-3p is increased in SMS-CTR ERMS cells expressing TPR-MET and downregulated in shMET RH30 ARMS cells in vitro, qPCR, n = 2–4. [score:7]
Those proangiogenic effects may be explained by enhanced expression of miR-378a, MMP9 and VEGF in SMS-CTR cells expressing TPR-MET, whereas antiangiogenic capabilities of ARMS cells with silenced MET level may be explained by decreased expression of those factors (Figure 7B). [score:7]
Moreover, inhibition of miR-378a with anti-miR-378a inhibitor reversed the effect of TPR-MET on VEGF mRNA and protein level (Figure 7C). [score:5]
In contrary, in rhabdomyosarcoma tumors miR-378 family members were demonstrated to be downregulated [40] and miR-378 was shown to induce myogenic differentiation by increasing the transcriptional activity of MyoD, in part by repressing an antagonist MyoR [41]. [score:4]
Activation of MET signaling in SMS-CTR ERMS cells induces proangiogenic effects in vitro by upregulation of miR-378, VEGF and MMP9, whereas MET silencing in RH30 ARMS exerts the opposite effects. [score:4]
C. Inhibition of miR-378a with anti-miR sequences reverses the effect of TPR-MET on VEGF mRNA and protein, n = 2–4. [score:3]
In our studies inhibition of miR-378a with anti-miR sequences reversed the effect of TPR-MET on VEGF level. [score:3]
In case of sarcomas miR-378* has been shown to be downregulated in osteosarcoma tumor compared to normal osteoblasts [39]. [score:3]
miR-378 can promote VEGF expression by competing with miR-125a for the same seed region in the VEGF 3′UTR [35]. [score:3]
In our studies we have observed only the influence of miR-378 on tumor vascularization and no effect on myogenic differentiation, probably because our SMS-CTR cell mo del does not display high MyoD expression. [score:3]
For evaluation of miRNA expression by quantitative real-time Sybr Green qPCR Master MIX (EURx) and universal reverse primer from NCode VILO miRNA cDNA Synthesis Kit (Invitrogen) were used with the following forward primers: U6 snRNA: 5-CGCAAGGATGACACGCAAA TTC-3′ miR-1: 5′-GCTGGAATGTAAAGAAGTATGT ATAA-3′ miR-206: 5-TGGAATGTAAGGAAGTGTGTGG-3′ miR-133a-5p: 5-GCAGCTGGTAAAATGGAACCA AAT-3′ miR-133a-3p: 5′-TGGTCCCCTTCAACCAGCTG-3′ miR-133b: 5′-TTTGGTCCCCTTCAACCAGCTA-3′ miR-378a-5p: 5′-CCTGACTCCAGGTCCTGTGT-3′ miR-378a-3p: 5′-ACTGGACTTGGAGTCAG AAGG-3′ The mRNA expression level for all samples was normalized to the housekeeping gene GAPDH, whereas miRNA level was normalized to the housekeeping U6 snRNA level. [score:1]
For evaluation of miRNA expression by quantitative real-time Sybr Green qPCR Master MIX (EURx) and universal reverse primer from NCode VILO miRNA cDNA Synthesis Kit (Invitrogen) were used with the following forward primers: U6 snRNA: 5-CGCAAGGATGACACGCAAA TTC-3′ miR-1: 5′-GCTGGAATGTAAAGAAGTATGT ATAA-3′ miR-206: 5-TGGAATGTAAGGAAGTGTGTGG-3′ miR-133a-5p: 5-GCAGCTGGTAAAATGGAACCA AAT-3′ miR-133a-3p: 5′-TGGTCCCCTTCAACCAGCTG-3′ miR-133b: 5′-TTTGGTCCCCTTCAACCAGCTA-3′ miR-378a-5p: 5′-CCTGACTCCAGGTCCTGTGT-3′ miR-378a-3p: 5′-ACTGGACTTGGAGTCAG AAGG-3′ The mRNA expression level for all samples was normalized to the housekeeping gene GAPDH, whereas miRNA level was normalized to the housekeeping U6 snRNA level. [score:1]
miR-378 has been previously demonstrated to induce progression and vascularization of many tumor types, both of epithelial and mesenchymal origin, such as, glioblastoma [36], non-small cell lung carcinoma [37] or breast cancer [38]. [score:1]
, Austin, TX, USA) against miR-378a-5p and miR-378a-3p and negative control using Lipofectamine 2000 (Invitrogen) according to the manufacturer's instructions 72 h before the experiments. [score:1]
Those results demonstrate for the first time that one of the proangiogenic mediators of the MET action may be miR-378. [score:1]
We hypothesize that miR-378 may be one of the mediators of proangiogenic and oncogenic actions of MET. [score:1]
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[+] score: 48
Therefore, we selected five DEMs, three upregulated (mmu-miR-192-5p, mmu-miR-291a-3p and mmu-miR-320-3p), and two downregulated (mmu-miR-139-5p and mmu-miR-378a-3p), construct miRNA-mRNA network to explore the regulatory mechanisms of miRNAs. [score:8]
In this study, we selected five DEMs, three upregulated (mmu-miR-192-5p, mmu-miR-291a-3p and mmu-miR-320-3p), and two downregulated (mmu-miR-139-5p and mmu-miR-378a-3p), to construct the miRNA-mRNA network (Figure 6). [score:7]
Red (mmu-miR-192-5p, mmu-miR-291a-3p and mmu-miR-320-3p) and Green (mmu-miR-139-5p and mmu-miR-378a-3p) are square nodes represent up-regulated and down-regulated miRNAs, respectively. [score:7]
The down-regulated expressed mmu-miR-378a-3p were selected for qRT-PCR validation, and the results showed a good consistency (Figure 5). [score:6]
miR-378a-3p promotes differentiation and inhibits proliferation of myoblasts by targeting HDAC4 in skeletal muscle development. [score:6]
In the miRNA and mRNA network diagram, another down-regulated miRNA miR-378a-3p, which verified by PCR and have a good consistency with the microarray results has been shown to function in regulating skeletal muscle growth and promoting the differentiation of myoblasts (Wei et al., 2016). [score:5]
Furthermore, the downregulated miRNAs mmu-miR-139-5p and mmu-miR-378a-3p were associated with 27 mRNAs and 9 mRNAs, respectively. [score:4]
Meanwhile, miR-378a plays an important role in adipogenesis and obesity, which can promote the adipogenesis of 3T3-L1 cells by targeting MAPK1 (Huang et al., 2015). [score:3]
MiR-378a-3p enhances adipogenesis by targeting mitogen-activated protein kinase 1. Biochem. [score:2]
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[+] score: 42
Using qPCR analysis to validate the results, we confirmed that miR-378 is up-regulated by E2 (Fig.   4B) and that this up-regulation is via the ESR1 pathway since E2 induction of miR-378 is not observed when MASE cells were pre -treated with an ESR1 antagonist (Fig.   4C). [score:7]
E2 suppresses Dab2 by up-regulation of miR-378. [score:6]
An E2 time-course experiment shows that E2 induction of miR-378 occurs within the same time frame as Dab2 transcript suppression (Fig.   4A,D) and using miRNA mimic assays, miR-378 was confirmed to be capable of suppressing DAB2 expression (Fig.   4E). [score:6]
Since our goal was to determine if miRNA up-regulation by E2 is a possible mechanism by which Dab2 can be decreased, we initially only focused on the top hit candidate miR-378, but it is nevertheless possible that Dab2 suppression is a combined effort among multiple miRNAs. [score:6]
Figure 4E2 suppresses Dab2 via up-regulation of miR-378. [score:6]
The ESR1 pathway mediates Dab2 suppression via E2 induction of miR-378, where Dab2 transcripts were significantly decreased within 3 h and maximal reduction in DAB2 protein was observed after 48 h. Finally, we have demonstrated that E2 suppression of Dab2 occurs both in vivo and in vitro, and across many cell types including mouse FTE and human ovarian and breast cancer cells. [score:5]
Of the miRNAs that had the highest increase in response to E2 (>2-fold change), miR-378 was the only miRNA that had a seeding sequence capable of targeting both human and mouse Dab2 transcripts (Supp. [score:3]
This is the first time miR-378 is reported to be E2 inducible via the ESR1 pathway and a regulator of Dab2. [score:2]
, n = 3. *p-value < 0.05 miR-378 significantly different relative to scrambled; two-way ANOVA. [score:1]
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[+] score: 34
Other miRNAs from this paper: hsa-mir-378a
Nodal expression in the placenta is suppressed by miRNA-378a-5p, which targets a region of the nodal 3′UTR. [score:7]
Mutations in the miRNA-378a-5p target site of the Nodal 3′-UTR can restore luciferase reporter expression. [score:6]
Stable transfection of miRNA-378a-5p in the human trophoblast cell line, HTR8/SV neo, decreases Nodal protein levels and represses expression of luciferase reporters harbouring Nodal 3′-UTR sequences, indicating that miRNA-378a-5p regulates Nodal protein translation. [score:6]
Indeed, experiments in Xenopus suggest that translation of the Nodal co-receptor Cripto is spatially regulated in the early frog embryo [92, 94] and dampening of Nodal signalling in the human placenta by miRNA-378a-5p is required for trophoblast proliferation and invasion. [score:4]
These findings suggest that repression of Nodal protein translation by miRNA-378a-5p might play an important role in human placental development. [score:4]
In the absence of miRNA-378a-5p, nodal translation is activated. [score:3]
In animal cap cells, xCR1 translation is activated in the absence of Bic-C. (c) miRNA-378a-5p (black comb) binds to the 3′-UTR (solid red box) of human Nodal RNA and unknown factors (?) [score:3]
In placental explants, the outgrowth of extravillous cytotrophoblasts is enhanced by miRNA-378a-5p, and it has been reported that miRNA-378a-5p levels are reduced in preterm pregnancies of pre-eclamptic women [32]. [score:1]
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[+] score: 31
Description miR-451[39] Upregulated in heart due to ischemia miR-22[40] Elevated serum levels in patients with stablechronic systolic heart failure miR-133[41] Downregulated in transverse aortic constrictionand isoproterenol -induced hypertrophy miR-709[42] Upregulated in rat heart four weeks after chronicdoxorubicin treatment miR-126[43] Association with outcome of ischemic andnonischemic cardiomyopathy in patients withchronic heart failure miR-30[44] Inversely related to CTGF in two rodent mo delsof heart disease, and human pathological leftventricular hypertrophy miR-29[45] Downregulated in the heart region adjacent toan infarct miR-143[46] Molecular key to switching of the vascular smoothmuscle cell phenotype that plays a critical role incardiovascular disease pathogenesis miR-24[47] Regulates cardiac fibrosis after myocardial infarction miR-23[48] Upregulated during cardiac hypertrophy miR-378[49] Cardiac hypertrophy control miR-125[50] Important regulator of hESC differentiation to cardiacmuscle(potential therapeutic application) miR-675[51] Elevated in plasma of heart failure patients let-7[52] Aberrant expression of let-7 members incardiovascular disease miR-16[53] Circulating prognostic biomarker in critical limbischemia miR-26[54] Downregulated in a rat cardiac hypertrophy mo del miR-669[55] Prevents skeletal muscle differentiation in postnatalcardiac progenitors To further confirm biological suitability of the identified miRNAs, we examined KEGG pathway enrichment using miRNA target genes (see ). [score:31]
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[+] score: 30
Eight miRNAs (miR-101, miR-107, miR-122, miR-29, miR-365, miR-375, miR-378, and miR-802), whose expression was found to be downregulated in c-Myc and/or AKT/Ras liver tumors, were selected and their tumor suppressor activity was assessed in c-Myc and AKT/Ras mice. [score:8]
miRNA Oncogene Growth Inhibition miR-101 c-Myc +++ AKT/Ras +++ miR-107 c-Myc + AKT/Ras ++ miR-122 c-Myc ++ AKT/Ras ++ miR-29 c-Myc ++ AKT/Ras + miR-365 c-Myc ++ AKT/Ras ++ miR-375 c-Myc + AKT/Ras +++ miR-378 c-Myc − AKT/Ras − miR-802 c-Myc ++ AKT/Ras − Taken together, the present results indicate that miR-378 does not possess tumor suppressor activity on c-Myc and AKT/Ras induced hepatocarcinogenesis in mice. [score:5]
Among all the miRNAs tested, overexpression of mir-378 had no or very limited activity in inhibiting c-Myc or AKT/Ras hepatocarcinogenesis in mice (Table 1 and Supplementary Figure 3A–3D). [score:5]
miRNA Oncogene Growth Inhibition miR-101 c-Myc +++ AKT/Ras +++ miR-107 c-Myc + AKT/Ras ++ miR-122 c-Myc ++ AKT/Ras ++ miR-29 c-Myc ++ AKT/Ras + miR-365 c-Myc ++ AKT/Ras ++ miR-375 c-Myc + AKT/Ras +++ miR-378 c-Myc − AKT/Ras − miR-802 c-Myc ++ AKT/Ras − Taken together, the present results indicate that miR-378 does not possess tumor suppressor activity on c-Myc and AKT/Ras induced hepatocarcinogenesis in mice. [score:5]
Indeed, when miR-378 was overexpressed in combination with c-Myc, all c-Myc/miR-378 injected mice developed palpable abdominal mass and became moribund by 6 weeks post injection. [score:3]
Lack tumor suppressor activity of miR-378 on c-Myc and AKT/Ras induced hepatocarcinogenesis. [score:3]
Similarly, all AKT/Ras/miR-378 injected mice developed lethal burden of liver tumors by 6.5 weeks post injection, and histologically AKT/Ras/miR-378 tumors were identical to AKT/Ras/pT3 tumors (Supplementary Figure 3A–3D). [score:1]
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[+] score: 28
Over -expression of miR-378 increased lipolysis genes expression, while inhibition of miR-378 expression attenuated stimulated lipolysis and reduced the expression of lipolytic regulators [44]. [score:12]
Moreover, miR-130b-MV injection increased the expression of miR-378a and miR-378-3p that are reported to participate in the regulation of fat deposition. [score:4]
For instance, miR-378a and miR-378b-3p were up-regulated significantly in the epididymal fat tissue of miR-130b-MV -injected mice. [score:4]
Over -expression of miR-378 was shown to increase fat accumulation [42], yet the opposite result was also reported [43]. [score:3]
The expression of miR-378a and miR-378b-3P was significantly increased (P < 0.05) in the epididymal fat of miR-130b-MV -injected mice when compared with miR-SC-MV -injected mice (Fig.   5). [score:2]
miR-378 is highly induced during adipogenesis and has been reported to be positively regulated in adipogenesis. [score:2]
The role of miR-378 family in fat deposition has been controversial. [score:1]
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18
[+] score: 28
We speculate that downregulation of miR-181b and miR-378* by baicalin may upregulate CPD removal via the NER signaling pathway. [score:7]
Three miRNAs (mmu-miR-378, mmu-miR-199a-3p and mmu-miR-181b) were downregulated and one (mmu-miR-23a) was upregulated in baicalin treated mice compared with UVB irradiated mice, and they were predicted to be related to DNA repair signaling pathway. [score:6]
Although there is no evidence that the Xpa gene is the direct target of miR-181b and miR-378*, the prediction of their target genes provides clues for further study. [score:6]
Other potentially important miRNAs downregulated by baicalin with UV irradiation were found in this study (i. e. mmu-miR-181b, mmu-miR-199a-3p, and mmu-miR-378). [score:4]
uk/), may be a target of miR-181b and miR-378*, and plays an important role in the NER signaling pathway. [score:3]
Four miRNAs (mmu-miR-23a, mmu-miR-378*, mmu-miR-199a-3p and mmu-miR-181b) were found to be differentially expressed in the UVB group compared with the baicalin plus UVB treated group (P < 0.05). [score:2]
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[+] score: 28
[29] ST2 stromal cells unknownInduced double-strand DNA breaks and reactive oxygen speciesaccumulation in transfected cells [30] miR-22-3p SIRT1 CDK6 SP1Induced growth suppression and acquisition of a senescentphenotype in human normal and cancer cells [31] human HDAC6Promoted osteogenic differentiation and inhibits adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells [32] human miR-31-5p RhoBTB1Repression of miR-31 inhibited colon cancer cell proliferation andcolony formation in soft agarose [33] HT29 cells unknownIs associated with marked change in the expression of specificmiRNA during aging in skeletal muscle [34] mouse miR-378-5p NephronectinGalNT-7Inhibited osteoblast differentiation [35] MC3T3-E1 miR-382-5p unknownDownregulated in skeletal muscle of old mice [34] mouseIn order to validate the sequencing data, we selected several miRNAs from Table 2 for additional qRT-PCR validation, which the minimum normalized read count of miRNAs was 5 in young, adult and old groups, including miR-210 [29], miR-22 [31], [32], miR-31 [36], [37], and miR-10b [16](Figure 3). [score:14]
[29] ST2 stromal cells unknownInduced double-strand DNA breaks and reactive oxygen speciesaccumulation in transfected cells [30] miR-22-3p SIRT1 CDK6 SP1Induced growth suppression and acquisition of a senescentphenotype in human normal and cancer cells [31] human HDAC6Promoted osteogenic differentiation and inhibits adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells [32] human miR-31-5p RhoBTB1Repression of miR-31 inhibited colon cancer cell proliferation andcolony formation in soft agarose [33] HT29 cells unknownIs associated with marked change in the expression of specificmiRNA during aging in skeletal muscle [34] mouse miR-378-5p NephronectinGalNT-7Inhibited osteoblast differentiation [35] MC3T3-E1 miR-382-5p unknownDownregulated in skeletal muscle of old mice [34] mouse In order to validate the sequencing data, we selected several miRNAs from Table 2 for additional qRT-PCR validation, which the minimum normalized read count of miRNAs was 5 in young, adult and old groups, including miR-210 [29], miR-22 [31], [32], miR-31 [36], [37], and miR-10b [16](Figure 3). [score:14]
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[+] score: 27
The expression of miR-378a-3p was down-regulated in both the NCTC and HepG2 cells, whereas it was up-regulated in the Hepa cells following exposure to 0.01 Gy irradiation (Supp. [score:9]
For example, miR-877-5p and miR-5114 were up-regulated, whereas miR-3963, miR-378a-3p, miR-193b-3p, miR-125a-5p, miR-378b, miR-365-3p, let-7e-5p, and miR-712-5p were down-regulated in the 0.01 Gy-irradiated mouse spleens compared with the sham spleens. [score:6]
To further study the regulation of miRNA expression, we first confirmed the expression of the miRNAs (miR-378a-3p, miR-193b-3p, and miR-125a-5p) in response to LDIR in a normal mouse liver cell line (NCTC), a mouse cancer cell line (Hepa), and a human hepatoma cell line (HepG2). [score:6]
Consistent with the results of the microarray analysis, the expression levels of miR-378a-3p, miR-193b-3p, miR-125a-5p, and miR-712-5p decreased in the 0.01 Gy-irradiated mouse spleens compared with the sham group, whereas the expression of miR-3963 did not change significantly. [score:4]
In our qRT-PCR analysis (Fig. 1A), only 5 miRNAs (miR-378a-3p, miR-193b-3p, miR-125a-5p, miR-712-5p, and miR-3963) generated acceptable Ct values, whereas the other 5 miRNAs (miR-877-5p, miR-5114, miR-378b, miR-365-3p, and let-7e-5p) fell below the minimum threshold because of their lower abundance. [score:1]
The levels of miR-378a-3p, miR-193b-3p, miR-125a-5p, and miR-712-5p decreased in response to LDIR, although the level of miR-3963 did not (Fig. 1B). [score:1]
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[+] score: 27
Figure 4. The ‘extended VCR’ of stratum 2 (shared by Homo and Pelodiscus sequences): (a) miR-16 target site (also shown in Fig. 2e) and nearby target sites for miR-376a, miR-335-3p, miR-493 and miR-379 (the Xenopus sequence contains a 44-bp insertion at the site of the asterisk that includes two target sites for miR-335-3p are shown in red); (b) conserved pair of target sites for miR-320a and miR-182; (c) conserved triplet of target sites for miR-378, miR-99a and miR-30aA notable feature of stratum 2 is a pair of complementary sequences, 800 nucleotides apart, that are predicted to form the stems of a strong double helix (18 bp, –32.3 kcal/mol). [score:11]
Figure 4. The ‘extended VCR’ of stratum 2 (shared by Homo and Pelodiscus sequences): (a) miR-16 target site (also shown in Fig. 2e) and nearby target sites for miR-376a, miR-335-3p, miR-493 and miR-379 (the Xenopus sequence contains a 44-bp insertion at the site of the asterisk that includes two target sites for miR-335-3p are shown in red); (b) conserved pair of target sites for miR-320a and miR-182; (c) conserved triplet of target sites for miR-378, miR-99a and miR-30a A notable feature of stratum 2 is a pair of complementary sequences, 800 nucleotides apart, that are predicted to form the stems of a strong double helix (18 bp, –32.3 kcal/mol). [score:11]
The megaloop contains, among other features, a conserved pair of target sites for miR-320a and miR-182 (Fig.  4b) and a conserved triplet of target sites for miR-378, miR-99a and miR-30a (Fig.  4c). [score:5]
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[+] score: 19
In TM4 cells exposed to NP, Ppara was down-regulated at both 3 and 24 h. We thus surmised that miRNAs regulated by Ppara may include miR-378, miR-125a-3p, and miRNA-148a at 3 h, and miR-20a, miR-203, and miR-101a at 24 h. Figure 3 Network analysis of miRNAs the expression of which in TM4 cells was altered by NP (A) 3 h. (B) 24 h. Network analysis was performed using an algorithm supported by IPA. [score:7]
In TM4 cells exposed to NP, Ppara was down-regulated at both 3 and 24 h. We thus surmised that miRNAs regulated by Ppara may include miR-378, miR-125a-3p, and miRNA-148a at 3 h, and miR-20a, miR-203, and miR-101a at 24 h. Figure 3 Network analysis of miRNAs the expression of which in TM4 cells was altered by NP (A) 3 h. (B) 24 h. Network analysis was performed using an algorithm supported by IPA. [score:7]
Network analysis of deregulated miRNAs suggested that Ppara may regulate the expression of certain miRNAs, including miR-378, miR-125a-3p miR-20a, miR-203, and miR-101a, after exposure to NP. [score:5]
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[+] score: 18
Among these dysregulated miRNAs, miR-378 was downregulated while miR-221 expression increased in aHSCs compared to qHSCs, consistent with previous reports 18, 19 and demonstrating the reliability of our microarray data. [score:6]
Moreover, miR-378a-3p has been shown to suppress the activation of HSCs by targeting Gli3, and injection of miR-378a-3p mimics into mice was shown to ameliorate chronic liver injury induced by CCl [4] [18]. [score:5]
Hyun J MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expressionNat. [score:4]
For example, Tu et al. [33] reported that lentivirus -mediated ectopic expression of miR-101 in liver greatly reduced CCl [4] -induced liver fibrosis and Hyun et al. [18] showed that systemic delivery of miR-378a-3p by nanoparticle technology significantly reduced hepatic damage. [score:3]
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[+] score: 18
Some of the results are in accordance with previous studies, such as the up-regulation of mmu-miR-221 and mmu-miR222 cluster and the down-regulation of the mmu-miR-200 family, as well as of mmu-miR-204, mmu-miR-30a*, mmu-miR-193, mmu-miR-378 and mmu-miR-30e*. [score:7]
The down-regulation of mmu-miR-30a*, mmu-miR-30e*, mmu-miR-193 and mmu-miR-378 during HFD -induced obesity is consistent with previous studies [19], [37], [50]. [score:4]
On the contrary, the following miRNAs were down-regulated in WAT after HFD feeding: mmu-miR-141, mmu-miR-200a, mmu-miR-200b, mmu-miR-200c, mmu-miR-122, mmu-miR-204, mmu-miR-133b, mmu-miR-1, mmu-miR-30a*, mmu-miR-130a, mmu-miR-192, mmu-miR-193a-3p, mmu-miR-203, mmu-miR-378 and mmu-miR-30e*. [score:4]
The following 22 murine microRNAs were selected for qPCR validation of their expression: mmu-miR-1, mmu-miR-21, mmu-miR-30a*, mmu-miR-30e*, mmu-miR-122, mmu-miR-130a, mmu-miR-133b, mmu-miR-141, mmu-miR-142-3p, mmu-miR-142-5p, mmu-miR-146a, mmu-miR-146b, mmu-miR-192, mmu-miR-193a-3p, mmu-miR-200b, mmu-miR-200c, mmu-miR-203, mmu-miR-204, mmu-miR-222, mmu-miR-342-3p, mmu-miR-378 and mmu-miR-379. [score:3]
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[+] score: 18
Figure 1(A) miRNA profiling showing miRNAs (103 upregulated and 72 downregulated) differentially expressed in miR-101 mimic -transfected SPAC-1-L cells compared with controls Venn diagram depicts overlapping miRNAs (let-7b, miR-361 and miR-378) that may be EZH2-regulated tumor suppressors. [score:11]
Of these, three (let-7, miR-361 and miR-378) were upregulated by EZH2 knockdown in DU145 prostate cancer cells [7], and were selected as the top candidates for further investigation (Figure 1A). [score:3]
Expression of let-7b (B), miR-361 (C) and miR-378 (D) as assessed by qRT-PCR in 24 EC and adjacent normal tissues. [score:3]
Lower let-7b (Figure 1E–1F) and miR-361 (Figure 1G–1H), but not miR-378 levels, were associated with worse outcomes (high-risk group). [score:1]
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[+] score: 17
Together with miR-378, another myofiber-enriched miRNA [37], we identified these miRNAs as the most upregulated in the serum of mice of the DAPC -associated pathologies, far beyond the FC level of the most downregulated miRNA. [score:7]
This included the markedly upregulated miR-378, which is another muscle-enriched miRNA [37] as well as miR-193b, miR-149 and miR-30a. [score:4]
Additionally the upregulation of miR-378 and its co-transcribed partner miR-378* were confirmed. [score:4]
The small DMD cohort studied here support further the relevance of these previously identified biomarkers as well as the newly identified miR-378, miR-378* and miR-31. [score:1]
In contrast, miR-378 was activated significantly at 22-weeks of age, but not at 4 weeks of age. [score:1]
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27
[+] score: 17
Other miRNAs from this paper: hsa-mir-25, hsa-mir-28, hsa-mir-95, mmu-mir-151, mmu-mir-290a, mmu-mir-297a-1, mmu-mir-297a-2, mmu-mir-130b, mmu-mir-340, mmu-mir-25, mmu-mir-28a, hsa-mir-130b, hsa-mir-367, hsa-mir-372, hsa-mir-378a, hsa-mir-340, hsa-mir-151a, mmu-mir-466a, mmu-mir-467a-1, hsa-mir-505, hsa-mir-506, mmu-mir-367, hsa-mir-92b, hsa-mir-548a-1, hsa-mir-548b, hsa-mir-548a-2, hsa-mir-548a-3, hsa-mir-548c, hsa-mir-648, hsa-mir-548d-1, hsa-mir-548d-2, hsa-mir-659, hsa-mir-421, hsa-mir-151b, hsa-mir-1271, hsa-mir-378d-2, mmu-mir-467b, mmu-mir-297b, mmu-mir-505, mmu-mir-297a-3, mmu-mir-297a-4, mmu-mir-297c, mmu-mir-421, mmu-mir-466b-1, mmu-mir-466b-2, mmu-mir-466b-3, mmu-mir-466c-1, mmu-mir-466e, mmu-mir-466f-1, mmu-mir-466f-2, mmu-mir-466f-3, mmu-mir-466g, mmu-mir-466h, mmu-mir-467c, mmu-mir-467d, mmu-mir-92b, mmu-mir-466d, hsa-mir-297, mmu-mir-467e, mmu-mir-466l, mmu-mir-669g, mmu-mir-466i, mmu-mir-466f-4, mmu-mir-466k, mmu-mir-467f, mmu-mir-466j, mmu-mir-467g, mmu-mir-467h, mmu-mir-1195, hsa-mir-548e, hsa-mir-548j, hsa-mir-1285-1, hsa-mir-1285-2, hsa-mir-1289-1, hsa-mir-1289-2, hsa-mir-548k, hsa-mir-1299, hsa-mir-548l, hsa-mir-1302-1, hsa-mir-1302-2, hsa-mir-1302-3, hsa-mir-1302-4, hsa-mir-1302-5, hsa-mir-1302-6, hsa-mir-1302-7, hsa-mir-1302-8, hsa-mir-548f-1, hsa-mir-548f-2, hsa-mir-548f-3, hsa-mir-548f-4, hsa-mir-548f-5, hsa-mir-1255a, hsa-mir-548g, hsa-mir-548n, hsa-mir-548m, hsa-mir-548o, hsa-mir-1268a, hsa-mir-548h-1, hsa-mir-548h-2, hsa-mir-548h-3, hsa-mir-548h-4, hsa-mir-548p, hsa-mir-548i-1, hsa-mir-548i-2, hsa-mir-548i-3, hsa-mir-548i-4, hsa-mir-1255b-1, hsa-mir-1255b-2, mmu-mir-1906-1, hsa-mir-1972-1, hsa-mir-548q, mmu-mir-466m, mmu-mir-466o, mmu-mir-467a-2, mmu-mir-467a-3, mmu-mir-466c-2, mmu-mir-467a-4, mmu-mir-466b-4, mmu-mir-467a-5, mmu-mir-466b-5, mmu-mir-467a-6, mmu-mir-466b-6, mmu-mir-467a-7, mmu-mir-466b-7, mmu-mir-467a-8, mmu-mir-467a-9, mmu-mir-467a-10, mmu-mir-466p, mmu-mir-466n, mmu-mir-466b-8, hsa-mir-3116-1, hsa-mir-3116-2, hsa-mir-3118-1, hsa-mir-3118-2, hsa-mir-3118-3, hsa-mir-548s, hsa-mir-378b, hsa-mir-466, hsa-mir-548t, hsa-mir-548u, hsa-mir-548v, hsa-mir-3156-1, hsa-mir-3118-4, hsa-mir-3174, hsa-mir-3179-1, hsa-mir-3179-2, hsa-mir-3179-3, hsa-mir-548w, hsa-mir-3156-2, hsa-mir-3156-3, hsa-mir-548x, mmu-mir-3470a, mmu-mir-3470b, mmu-mir-3471-1, mmu-mir-3471-2, hsa-mir-378c, hsa-mir-1972-2, hsa-mir-1302-9, hsa-mir-1302-10, hsa-mir-1302-11, mmu-mir-1906-2, hsa-mir-3683, hsa-mir-3690-1, hsa-mir-548y, hsa-mir-548z, hsa-mir-548aa-1, hsa-mir-548aa-2, hsa-mir-548o-2, hsa-mir-1268b, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-548h-5, hsa-mir-548ab, hsa-mir-378f, hsa-mir-378g, hsa-mir-548ac, hsa-mir-548ad, hsa-mir-548ae-1, hsa-mir-548ae-2, hsa-mir-548ag-1, hsa-mir-548ag-2, hsa-mir-548ah, hsa-mir-378h, hsa-mir-548ai, hsa-mir-548aj-1, hsa-mir-548aj-2, hsa-mir-548x-2, hsa-mir-548ak, hsa-mir-548al, hsa-mir-378i, hsa-mir-548am, hsa-mir-548an, mmu-mir-28c, mmu-mir-378b, mmu-mir-28b, hsa-mir-548ao, hsa-mir-548ap, mmu-mir-466q, hsa-mir-548aq, hsa-mir-548ar, hsa-mir-548as, hsa-mir-548at, hsa-mir-548au, hsa-mir-548av, hsa-mir-548aw, hsa-mir-548ax, hsa-mir-378j, mmu-mir-378c, mmu-mir-378d, hsa-mir-548ay, hsa-mir-548az, hsa-mir-3690-2, mmu-mir-290b, hsa-mir-548ba, hsa-mir-548bb, hsa-mir-3179-4, mmu-mir-466c-3, hsa-mir-548bc, mmu-mir-1271
In the miR-378 network (Figure 8A), ERBB2 is a transcription factor of the miR-378 gene and it's host gene PPARGC1B which encodes PGC-1β [73] and HNE, which it also appears, could downregulate miR-378 and induce the expression of its target gene, SuFu [74]. [score:8]
The expression of miR-378* increases during breast cancer progression and miR-378* induces the Warburg effect in breast cancer cells by inhibiting the expression of two PGC-1 partners, ERR and GABPA [73]. [score:7]
0017666.g008 Figure 8 (A) miR-378 (RdmiR, mir-378 family). [score:1]
The functional networks of miR-92b (PRdmiR, mir-25 family, derived from GC rich tandem repeats), miR-28 (RdmiR, mir-28 family, derived from LINE), miR-151 (RdmiR, mir-28 family, derived from LINE), miR-421 (RdmiR, mir-95 family, derived from LINE), miR-1271 (RdmiR, mir-1271 family, derived from LINE), miR-340 (RdmiR, mir-340 family, derived from DNA transportable element) and miR-378 (RdmiR, mir-378 family, derived from SINE) have been reconstructed (Figure 8). [score:1]
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[+] score: 16
Aromatase expression and subsequent E [2] production by GCs are directly post-transcriptionally downregulated by miR-378 [19]. [score:7]
In porcine GCs, miR-378 is spatiotemporally expressed and shows an inverse expression pattern to that of aromatase. [score:5]
The Cyp19a1 gene has also been confirmed to be a direct target of miR-378 [17] and miR-98 [18]. [score:4]
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[+] score: 14
These include the miR-130 family members that repress brown and white adipogenesis via direct inhibition of Pparg [30] and miR-378 that activates Cebpa and Cebpb expression during adipogenesis and enhances brown fat expansion [31, 32]. [score:6]
In concert with this, the expression of miR-378 was at the same level in Fto- KO BAT of mice fed either diet while in the WT BAT, miR-378 was decreased by 1.4-fold after HFD. [score:3]
Gerin I. Bommer G. T. McCoin C. S. Sousa K. M. Krishnan V. MacDougald O. A. Roles for miRNA-378/378* in Adipocyte Gene Expression and Lipogenesis Am. [score:3]
In addition, miR-378 was reported to activate C/EBPs during adipogenesis and enhance BAT expansion [31, 35]. [score:1]
miR-378 has been shown to activate Cebpa and Pparg [31, 35]. [score:1]
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30
[+] score: 12
In addition to well-known myomiRs, recent studies have demonstrated that miR-486 [49], miR-378 [50], miR181a [80], miR-21a, miR-101a, and miR-151 [54] are also involved in regulation of myogenesis and several other ubiquitously expressed miRNAs have also been found to participate in myogenesis, including miR-26a [51], miR-27b [52, 53], and miR-29 [44]. [score:4]
A total of 57 differentially expressed miRNAs were identified; out of these miR-133a, miR-378a, and miR-26 were highly abundant. [score:3]
The predominance of miR-133a was consistent with its well established function during skeletal muscle development; miR-378a is also reported to play important role during Mus musculus myogenesis. [score:2]
MiR-133a [23, 38], miR-378a [50], miR-26a [51], miR-27b [52, 53], miR-21a [56], miR-29a [44], miR-148 [58], and miR-103 are skeletal muscle specific miRNAs and play a vital role in muscle differentiation and proliferation as reported in previous studies. [score:1]
Out of 8 known miRNAs, 6 miRNAs have been functionally linked to myogenesis (i. e., miR-1a, miR-26a, miR-133a and miR-199a, miR-101, and miR-378 [38, 50, 51, 54, 55, 70]). [score:1]
Of the 8 known miRNAs examined, 7 miRNAs (miR-425, miR-26a, miR-1a, miR-199a, miR-101, miR-378, and miR-151) showed a consistent pattern with the deep sequencing data (Figures 6(a)– 6(j)). [score:1]
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31
[+] score: 11
Song GS et al reported that miR-378 plays critical roles during the early phase of LR by directly inhibiting the expression of Odc1, which is associated with DNA synthesis [12]– [13]. [score:6]
In our preliminary study, using a quantitative real-time PCR analysis, we found that, like miR-378, miR-26a expression was obviously down-regulated in regenerating mice liver tissue at 120 h after 70% PH, compared with the sham operation (SH) group. [score:5]
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[+] score: 10
CD3 [+] peripheral T lymphocytes exhibited two modulated miRNAs, miR-296-5p (down-regulated) and miR-378 (up-regulated), and PILs exhibited seven upregulated miRNAs (miR 202-3p, miR 709, miR 10b*, miR 705, miR 697, miR 712 and miR 877). [score:10]
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[+] score: 10
These results are consistent with previous studies demonstrating that miR-378a-3p expression is reduced in tumor tissue from BrCa patients and its expression is associated with better prognosis in BrCa patients treated with hormone therapy [29]. [score:5]
We demonstrated that CTBP1 represses miR-378a-3p and miR-494-3p and induces miR-146a-5p and let-7e-3p expression in MDA-MB-231 xenografts. [score:3]
We identified a cluster of miRNAs with relevant roles in cell proliferation (miR-378a-3p, miR-146a-5p and miR-381) and tumor progression (miR-378a-3p, miR-146a-5p, miR-381, miR-223-3p, miR-494-3p, miR-940, miR-433, miR-522 and miR-637) (Supplementary Table 1). [score:1]
As shown in Figure 3B, using miRNA RT-qPCR we found that CTBP1 modulated miR-494-3p, miR-381-5p, miR-378a-3p, let-7e-3p, miR-194-1-5p and miR-146a-5p in MDA-MB-231-derived xenografts (Figure 3B). [score:1]
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[+] score: 9
MiRNA target site/Species Human Mouse Cow Dog Chicken FrogTargeting Twist2 miR-15b-3p + − + + − − − miR-33-5p + + + + − + − miR-137-3p + + + + − + − miR-145a-5p + + + + − − + miR-151-5p + + + + − + − miR-214-5p + + + + − − − miR-326-3p + + + + − − − miR-337-3p + + + + − + − miR-361-5p + + + + − − − miR-378a-5p + + + + − − − miR-381-3p + + + + − + − miR-409-3p + + + + − − − miR-450b-5p + + + + − + − miR-508-3p + + + + − − − miR-543-3p + + + + − − − miR-576-5p + + + + − − − miR-580 + + + + − − − miR-591 + + + + − − − MicroRNAs underlined were tested in this study. [score:5]
The following miRNAs were tested for their potential to repress Twist1 translation in the human lung carcinoma cell line H1299: miR-33, miR-145a, miR-151, miR-326, miR-337, miR-361, miR-378a, miR-381, miR-409 and miR-543 (Fig. 1). [score:3]
The miRBase accession numbers for miRNAs are: mmu-miR-33 (MI0000707), mmu-miR-145a (MI0000169), mmu-miR-151 (MI0000173), mmu-miR-326 (MI0000598), mmu-miR-337 (MI0000615), mmu-miR-361 (MI0000761), mmu-miR-378a (MI0000795), mmu-miR-381 (MI0000798), mmu-miR-409 (MI0001160) and mmu-miR-543 (MI0003519). [score:1]
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35
[+] score: 9
For example, the human miRNA has-miR-378 is predicted to have a target site in the mRNA corresponding to human gene BCL7A, while mmu-miR-378, the mouse ortholog of has-miR-378, has a target site in the mRNA for Bcl7a (the orthologous gene in mouse). [score:5]
We thus consider the has-miR-378 target site in BCL7A to have an ortholog in mouse, and infer that regulation of these genes by this miRNA has been evolutionarily conserved between human and mouse. [score:4]
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[+] score: 9
No expression was observed for miR-122 and miR-378 (data not shown). [score:3]
Gene expression data from human CE-RSCs from adult eyes were also analysed and although many different miRNAs were predicted to be affecting mRNA levels, it was notable that the two miRNAs with the most significant effects in murine CE-RSCs, miR-378 and miR-485-3p, were also the 3 [rd ]and 4 [th ]most significant in human CE-RSCs (Additional file 1: Table S1). [score:3]
Whilst most of the candidate miRNAs predicted to affect mRNA levels (P < 0.05) at P4 were also in the adult, only miR-125, miR-378 and miR-24 were detected in all the different tissue types and developmental stages. [score:2]
A range of other candidates with p-values < 0.05 in at least one experimental condition (miR-128, miR-150, miR-204, miR-25, miR-27, miR-326 miR-34, miR-370, miR-378 and miR-485-5p) were selected to represent different predicted patterns of activity or for their lack of previous association with neural tissue. [score:1]
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[+] score: 9
A group of 39 miRNAs was significantly down-regulated by Nkx2-1 knock-down including miR-1195 (−4.9 fold), miR-378 (−4.6 fold), miR-449a (−2.1 fold), and miR-130a (−1.9 fold) (Figure  2A and Table  1). [score:5]
Expression patterns of the most altered miRNAs (miR-200c, miR-221, miR-1195, and miR-378) were analyzed in Nkx2-1 knock-down cells by RT-qPCR (Figure  2B) confirming the microarray data. [score:4]
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[+] score: 8
Finally, miR-378 increases brown fat mass and as a consequence, suppresses development of beige adipocytes in subcutaneous WAT [23]. [score:4]
Several miRNAs controlling mouse brown adipocyte development and function have been identified in mice, including miR-27, −34a, −133, −155, −182, −193b-365, −196, −203 and miR-378 [14, 16– 23]. [score:2]
This phenotype is supported by the absence of miR-378, a key regulator controlling classical BAT-specific expansion and obesity resistance [23]. [score:2]
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[+] score: 8
Other miRNAs from this paper: mmu-let-7c-2, mmu-mir-17, mmu-mir-378b, mmu-mir-378c, mmu-mir-378d
Furthermore, mature microRNA miR-378*, recently shown to act as a negative regulator of the TCA cycle and oxidative metabolism by down -regulating ERRγ and GABPA expression [38] was also found to have an altered diurnal expression in ERRα -null mice (Figure S1A). [score:7]
microRNA levels were detected and normalized to snoRNA412 levels using Taqman miRNA RT-PCR following the manufacturer's instructions (Applied Biosystems, snoRNA412 #1243, miR-122a #2245, miR-378* #567). [score:1]
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[+] score: 8
Furthermore, Th2-type inflammation induces macrophage proliferation and anti-proliferative miR-378 expression simultaneously, suggesting a complex regulation of in situ macrophage proliferation [19]. [score:4]
For instance, miR-125b-5p, miR-199b, and miR-378-3p showed elevated expression in nematode infection-elicited alternative macrophage activation [19]. [score:3]
Among these miRNAs, miR-378-3p has been shown to repress IL-4 -driven macrophage proliferation through the modulation of the PI3K/AKT signaling pathway [19]. [score:1]
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[+] score: 8
The high abundance of mmu-miR-378a in the brain was surprising as this miRNA has not been reported to be highly expressed in the nervous system. [score:3]
In the adult brain, we find mmu-miR-378a edited to 6.2% at position 16 (Table 4), verifying that editing efficiency of this miRNA increases during development. [score:2]
Also, in a previous study we detected very low editing of this mmu-miR-378a at embryonic day 11.5 (29). [score:1]
This group of miRNAs consisted of the same members in all replicates and in both genotypes with mmu-miR-378a being most abundant. [score:1]
Mmu-miR-378a had already been reported by others to be edited (18, 38). [score:1]
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[+] score: 7
Overexpression of miR-802 impairs glucose metabolism [35] miR-378 is regulated by glucose concentration, while high level of miR-378 could attenuates high glucose -suppressed osteogenic differentiation in vitro and diabetic mice mo del [36]. [score:6]
In them, 9 miRNAs (miR-21a, miR-29c, miR-30a, miR-30b, miR-34a, miR-106b, miR-203, miR-378 and miR-802) had been shown to be related with diabetes or glucose metabolism. [score:1]
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[+] score: 7
Other miRNAs from this paper: mmu-let-7g, mmu-let-7i, mmu-mir-23b, mmu-mir-29b-1, mmu-mir-30b, mmu-mir-99a, mmu-mir-126a, mmu-mir-132, mmu-mir-141, mmu-mir-181a-2, mmu-mir-185, mmu-mir-193a, mmu-mir-199a-1, mmu-mir-200b, mmu-mir-34c, mmu-let-7d, mmu-mir-196a-1, mmu-mir-196a-2, mmu-mir-200a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-20a, mmu-mir-22, mmu-mir-23a, mmu-mir-26a-1, mmu-mir-26b, mmu-mir-34a, mmu-mir-200c, mmu-mir-212, mmu-mir-181a-1, mmu-mir-26a-2, mmu-mir-29b-2, mmu-mir-199a-2, mmu-mir-199b, mmu-mir-451a, mmu-mir-674, mmu-mir-423, mmu-mir-146b, bta-mir-26a-2, bta-let-7f-2, bta-mir-16b, bta-mir-20a, bta-mir-26b, bta-mir-99a, bta-mir-126, bta-mir-181a-2, bta-mir-199a-1, bta-mir-30b, bta-mir-193a, bta-let-7d, bta-mir-132, bta-mir-199b, bta-mir-200a, bta-mir-200c, bta-mir-22, bta-mir-23a, bta-mir-29b-2, bta-mir-423, bta-let-7g, bta-mir-200b, bta-let-7a-1, bta-let-7f-1, bta-let-7i, bta-mir-23b, bta-mir-34c, bta-let-7a-2, bta-let-7a-3, bta-let-7b, bta-let-7c, bta-let-7e, bta-mir-34a, bta-mir-141, bta-mir-146b, bta-mir-16a, bta-mir-185, bta-mir-196a-2, bta-mir-196a-1, bta-mir-199a-2, bta-mir-212, bta-mir-26a-1, bta-mir-29b-1, bta-mir-181a-1, bta-mir-2284i, bta-mir-2284s, bta-mir-2284l, bta-mir-2284j, bta-mir-2284t, bta-mir-2284d, bta-mir-2284n, bta-mir-2284g, bta-mir-2284p, bta-mir-2284u, bta-mir-2284f, bta-mir-2284a, bta-mir-2284k, bta-mir-2284c, bta-mir-2284v, bta-mir-2284q, bta-mir-2284m, bta-mir-2284b, bta-mir-2284r, bta-mir-2284h, bta-mir-2284o, bta-mir-2284e, bta-mir-2284w, bta-mir-2284x, bta-mir-2284y-1, mmu-let-7j, bta-mir-2284y-2, bta-mir-2284y-3, bta-mir-2284y-4, bta-mir-2284y-5, bta-mir-2284y-6, bta-mir-2284y-7, bta-mir-2284z-1, bta-mir-2284aa-1, bta-mir-2284z-3, bta-mir-2284aa-2, bta-mir-2284aa-3, bta-mir-2284z-4, bta-mir-2284z-5, bta-mir-2284z-6, bta-mir-2284z-7, bta-mir-2284aa-4, bta-mir-2285t, bta-mir-2284z-2, mmu-let-7k, mmu-mir-126b, bta-mir-2284ab, bta-mir-2284ac
For example, miR-146b-5p and miR-378a-3p were highly expressed in mouse but they were present at a low level of expression in bovine; inversely, miR-199b-5p, miR-423-5p and miR-193a-5p were weakly expressed in mouse but highly in bovine (Table S2). [score:7]
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[+] score: 7
The comparison between control- and MPA -treated cells revealed that 16 miRNAs were significantly modulated by more than two-fold (P < 0.05, Figure 1A), nine miRNAs were upregulated (miR-191*, miR-17*, miR- 470*, miR-451, miR-702, miR-434-3p, miR-493, miR-23a* and miR-485*) and seven were downregulated (miR-378*, miR-376a, miR-224, miR-190b, miR-16, miR-410 and miR-197) (Figure 1B). [score:7]
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[+] score: 6
Among the targets for differentially expressed miRNAs, mmu-miR-378 had important roles in immune function (involved in natural killer cell mediated cytotoxicity, T cell receptor and B cell receptor signaling pathway in miR-497), signal pathway induction (involved in the calcium signaling pathway, ErbB signaling pathway, MAPK signaling pahtway), and nutrition metabolism (involved in GnRH signaling pathway and the insulin signaling pathway). [score:5]
The mTOR signaling pathway was correlated with miR-26b, while miR-378 mediated natural killer cell cytotoxicity and TCR signaling pathway. [score:1]
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[+] score: 6
Other miRNAs from this paper: mmu-mir-200a, mmu-mir-17, mmu-mir-378b, mmu-mir-378c, mmu-mir-378d
Our results supported by those of Kahai et al. showing that UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7 (GalNAc-T7) is inhibited by miR-378 with consequences in the rate of osteoblast differentiation [31], open new and interesting perspectives, as the regulation of proteins involved in N-glycosylation (and potentially any other post-translational modification) of antithrombin (and extensively other proteins) may be done by miRNAs. [score:6]
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[+] score: 6
For the LRGA, 0.2 μg of each pmirGLO construct was transfected together with 1.6 pmol of miR-let-7a, miR-378, or a scrambled miRNA (Thermo Scientific Dharmacon, Waltham, MA, USA) into HEK-293T cells (6 × 10 [4] cells/well) in a 96-well plate. [score:1]
We confirmed that miR-let-7a interacted with the Hmga2 3′ UTR and that miR-378 interacted with the Prpsap1 3′ UTR. [score:1]
Here, 15 miRNAs (miR-let-7e*, miR-15a*, miR-19b-1*, miR-30e*, miR-130b*, miR-149, miR-296-5p, miR-362-5p, miR-378, miR-425, miR-432, miR-484, miR-574-3p, miR-671-5p, and miR-1249) established interactions with 19 mRNAs. [score:1]
The highlighted interaction (miR-378–Prpsap1 mRNA) was selected for further validations. [score:1]
pMIR-Hmga2 or pMIR-Hmga2 (M) 3′ UTR luciferase plasmid were co -transfected with control irrelevant miR or with miR-let-7a mimic (A), pMIR-Prpsap1 or pMIR-Prpsap (m) plasmid were co -transfected with control irrelevant miR or with miR-378 mimic (B) into HEK-293T cells. [score:1]
We choose the miR-let-7a–Hmga2 mRNA and miR-378–Prpsap1 mRNA interactions for validation through LGRA because these mRNAs encoded PTAs and therefore could be adequately used as references (Figures 6A,B). [score:1]
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[+] score: 6
To further assess the alterations of mitochondria-related miRNAs in obesity, we examined the expression levels of miR-126a-3p, miR-141-3p, miR-196a-5p, miR-210-3p, miR-378a-3p, miR-484 and miR-499a-5p in mice livers. [score:3]
As shown in Fig. 2G, the expression of mitochondria-related miR-141-3p was strikingly increased and miR-196a-5p, miR-210-3p, miR-378a-3p were reduced in the HFD mice. [score:3]
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49
[+] score: 6
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-20a, hsa-mir-22, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-98, hsa-mir-101-1, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-15b, mmu-mir-101a, mmu-mir-126a, mmu-mir-130a, mmu-mir-133a-1, mmu-mir-142a, mmu-mir-181a-2, mmu-mir-194-1, hsa-mir-208a, hsa-mir-30c-2, mmu-mir-122, mmu-mir-143, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-181a-1, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-122, hsa-mir-130a, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-142, hsa-mir-143, hsa-mir-126, hsa-mir-194-1, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-208a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-18a, mmu-mir-20a, mmu-mir-22, mmu-mir-26a-1, mmu-mir-26b, mmu-mir-29c, mmu-mir-98, mmu-mir-326, rno-mir-326, rno-let-7d, rno-mir-20a, rno-mir-101b, mmu-mir-101b, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-181b-2, mmu-mir-17, mmu-mir-19a, mmu-mir-181a-1, mmu-mir-26a-2, mmu-mir-19b-1, mmu-mir-181b-1, mmu-mir-181c, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-101-2, hsa-mir-26a-2, hsa-mir-378a, hsa-mir-326, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-181b-2, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-15b, rno-mir-16, rno-mir-17-1, rno-mir-18a, rno-mir-19b-1, rno-mir-19a, rno-mir-22, rno-mir-26a, rno-mir-26b, rno-mir-29c-1, rno-mir-30c-1, rno-mir-30c-2, rno-mir-98, rno-mir-101a, rno-mir-122, rno-mir-126a, rno-mir-130a, rno-mir-133a, rno-mir-142, rno-mir-143, rno-mir-181c, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-194-1, rno-mir-194-2, rno-mir-208a, rno-mir-181a-1, hsa-mir-423, hsa-mir-18b, hsa-mir-20b, hsa-mir-451a, mmu-mir-451a, rno-mir-451, ssc-mir-122, ssc-mir-15b, ssc-mir-181b-2, ssc-mir-19a, ssc-mir-20a, ssc-mir-26a, ssc-mir-326, ssc-mir-181c, ssc-let-7c, ssc-let-7f-1, ssc-let-7i, ssc-mir-18a, ssc-mir-29c, ssc-mir-30c-2, hsa-mir-484, hsa-mir-181d, hsa-mir-499a, rno-mir-1, rno-mir-133b, mmu-mir-484, mmu-mir-20b, rno-mir-20b, rno-mir-378a, rno-mir-499, hsa-mir-378d-2, mmu-mir-423, mmu-mir-499, mmu-mir-181d, mmu-mir-18b, mmu-mir-208b, hsa-mir-208b, rno-mir-17-2, rno-mir-181d, rno-mir-423, rno-mir-484, mmu-mir-1b, ssc-mir-15a, ssc-mir-16-2, ssc-mir-16-1, ssc-mir-17, ssc-mir-130a, ssc-mir-101-1, ssc-mir-101-2, ssc-mir-133a-1, ssc-mir-1, ssc-mir-181a-1, ssc-let-7a-1, ssc-let-7e, ssc-let-7g, ssc-mir-378-1, ssc-mir-133b, ssc-mir-499, ssc-mir-143, ssc-mir-423, ssc-mir-181a-2, ssc-mir-181b-1, ssc-mir-181d, ssc-mir-98, ssc-mir-208b, ssc-mir-142, ssc-mir-19b-1, hsa-mir-378b, ssc-mir-22, rno-mir-126b, rno-mir-208b, rno-mir-133c, hsa-mir-378c, ssc-mir-194b, ssc-mir-133a-2, ssc-mir-484, ssc-mir-30c-1, ssc-mir-126, ssc-mir-378-2, ssc-mir-451, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, mmu-mir-378b, mmu-mir-101c, hsa-mir-451b, hsa-mir-499b, ssc-let-7a-2, ssc-mir-18b, hsa-mir-378j, rno-mir-378b, mmu-mir-133c, mmu-let-7j, mmu-mir-378c, mmu-mir-378d, mmu-mir-451b, ssc-let-7d, ssc-let-7f-2, ssc-mir-20b-1, ssc-mir-20b-2, ssc-mir-194a, mmu-let-7k, mmu-mir-126b, mmu-mir-142b, rno-let-7g, rno-mir-15a, ssc-mir-378b, rno-mir-29c-2, rno-mir-1b, ssc-mir-26b
miR-101, miR-378 and 143 expression patterns. [score:3]
The expression of miR-378 was highly variable among the tissues tested (Figure 2E). [score:3]
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Other Rac1-miR-CATCH-captured miRNAs, which were not predicted to target Rac1 included miR-125a/b-5p, miR-378a-3p and miR-204-5p; all of which had ≥4-fold enrichment (Table 3b). [score:3]
Notably, in silico prediction tools had not predicted a number of miRNAs to target Rac1 (e. g. miR-125a/b-5p, miR-378a-3p and miR-204-5p), yet they were enriched in Rac1-miR-CATCH capture versus control samples (Table 3b). [score:3]
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Nine miRNAs (miR-148a-3p, miR-183a-5p, miR-214-3p, miR-27a-3p, miR-92a-3p, miR-378a-3p, miR-23a-3p, miR-21a-5p and miR-16-5p) were upregulated, and four (miR-155-5p, miR-199a-3p, miR-320-3p and miR-125a-5p) were downregulated in exosomes from RANKL -induced RAW 264.7 cells compared with RAW 264.7 cells (Figure 1f and Supplementary Figure S1d). [score:6]
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[+] score: 5
Interestingly, the certain miRNAs, such as miR-96, miR-140, miR-151, miR-185, miR-378, miR-455, miR-532, and miR-874, presumably targeting a 3’UTR of INSR, were upregulated by more than 1.5-fold in the liver of HFD mice compared to NFD-fed control, whereas the levels of other selected miRNAs remained unaffected (S2 Fig). [score:5]
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Others, including let-7f, miR-27b [6], miR-221, and miR-222 [12], have been shown to modulate angiogenesis in vitro and overexpression or inhibition of miR-378 [13], the miR-17-92 cluster [14] and miR-296 [15] affects angiogenesis in mouse engrafted tumors. [score:5]
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In contrast, miR-378a negatively affects the remo delling phase, delaying the healing of mouse skin wounds by downregulating β3 integrin and vimentin [29]. [score:4]
Some notable examples include miR-130a, miR-132, miR-155, miR-198, miR-21, miR-31 and miR-378a 13, 23, 24, 26, 28– 30. miR-155 acts as an important player in controlling the inflammatory response during skin repair; genetic deletion of miR-155 in mice leads to accelerated healing associated with elevated numbers of macrophages and increased type-1 collagen deposition in wounded tissue [30]. [score:1]
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A further differentially expressed miRNA whose target mRNA profile was not statistically significant, miR-378, is known to promote angiogenesis [62]. [score:5]
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They found that miR-320, miR-378, miR-211, miR-200a,b and miR-184 were significantly down-regulated during both stages of hibernation compared with non-hibernating animals, whereas miR-486, miR-451, miR-144 and miR-142 were significantly overexpressed in late torpor phase [22]. [score:5]
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[+] score: 4
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-17, hsa-mir-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-27a, hsa-mir-30a, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-107, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-30a, mmu-mir-30b, mmu-mir-125b-2, mmu-mir-9-2, mmu-mir-150, mmu-mir-24-1, mmu-mir-204, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-204, hsa-mir-210, hsa-mir-221, hsa-mir-222, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-125b-1, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-150, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-21a, mmu-mir-24-2, mmu-mir-27a, mmu-mir-103-1, mmu-mir-103-2, mmu-mir-326, mmu-mir-107, mmu-mir-17, mmu-mir-210, mmu-mir-221, mmu-mir-222, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-125b-1, hsa-mir-30c-1, hsa-mir-30e, hsa-mir-378a, hsa-mir-326, ssc-mir-125b-2, ssc-mir-24-1, ssc-mir-326, ssc-mir-27a, ssc-let-7c, ssc-let-7f-1, ssc-let-7i, ssc-mir-103-1, ssc-mir-107, ssc-mir-204, ssc-mir-21, ssc-mir-30c-2, ssc-mir-9-1, ssc-mir-9-2, hsa-mir-378d-2, hsa-mir-103b-1, hsa-mir-103b-2, ssc-mir-15a, ssc-mir-17, ssc-mir-30b, ssc-mir-210, ssc-mir-221, ssc-mir-30a, ssc-let-7a-1, ssc-let-7e, ssc-let-7g, ssc-mir-378-1, ssc-mir-30d, ssc-mir-30e, ssc-mir-103-2, ssc-mir-27b, ssc-mir-24-2, ssc-mir-222, ssc-mir-125b-1, hsa-mir-378b, hsa-mir-378c, ssc-mir-30c-1, ssc-mir-378-2, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, mmu-mir-378b, ssc-let-7a-2, hsa-mir-378j, mmu-mir-21b, mmu-let-7j, mmu-mir-378c, mmu-mir-21c, mmu-mir-378d, mmu-mir-30f, ssc-let-7d, ssc-let-7f-2, ssc-mir-9-3, ssc-mir-150-1, ssc-mir-150-2, mmu-let-7k, ssc-mir-378b, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
We found 13 adipogenesis-promoting miRNAs (let-7、miR-9、miR-15a、miR-17、miR-21、miR-24、miR-30、miR-103、miR-107、miR-125b、miR-204、miR-210、and miR-378) target 860 lncRNA loci. [score:3]
We analyzed the relationship between the 343 identified lncRNAs with the 13 promoting adipogenesis miRNAs (let-7、miR-9、miR-15a、miR-17、miR-21、miR-24、miR-30、miR-103、miR-107、miR-125b、miR-204、miR-210、and miR-378) and five depressing adipogenesis miRNAs (miR-27, miR-150, miR-221, miR-222, and miR-326). [score:1]
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[+] score: 4
Growing evidence shows that miRs are involved in obesity and obesity-related metabolic disorders [9], such as miR-223 [10], miR-378 [11], and miR-103/107 [12]. [score:1]
Consistent with our finding, impaired energy expenditure was observed in mice lacking miR-378/378* [11] and in miR-196 transgenic mice [32]. [score:1]
Mice lacking miR-378/378* are lean and resistant to HFD -induced obesity, whereas our AS KO mice are sensitive to diet -induced obesity. [score:1]
Similar to other mouse strains carrying a global deletion of miR-378/378* [11], our AS KO mice exhibited overt phenotypes in response to excessive calorie intake. [score:1]
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Similarly, miR-181c and miR-378 regulated mitochondria targets in cardiomyocytes, leading to alteration in electron transport chain, fatty acid metabolism, and apoptosis under metabolic stress [14– 16]. [score:4]
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[+] score: 4
Other miRNAs from this paper: mmu-mir-200a, mmu-mir-378b, mmu-mir-378c, mmu-mir-378d
Hyun J MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expressionNat. [score:4]
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61
[+] score: 3
The expression level of 9 miRNAs changed significantly between F1 and F3 (F1F3: hsa-miR-378, 422b, and 768-5p). [score:3]
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62
[+] score: 3
Other miRNAs from this paper: mmu-mir-193a, mmu-mir-193b, mmu-mir-378b, mmu-mir-378c, mmu-mir-378d
Finally, we profiled microRNA gene expression along the same process, leading to the identification of known general adipogenic microRNAs (e. g. miR-378), brown lineage-specific microRNAs (miR-193), as well as several microRNAs not implicated in adipogenesis so far (S5 Fig and S2 Table). [score:3]
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63
[+] score: 3
Specific miRNAs that enhance adipocyte differentiation (miR-30c, miR-143, miR-146b, and miR-378; [21– 24]) or inhibit adipocyte differentiation (miR-27, miR-130, and miR-138; [25– 27]) have been identified. [score:3]
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Previous studies have demonstrated that the myomiRs miR-1, miR-133a/b, miR-206, miR-486, miR-26a, miR-27b, miR-378, miR-148a and miR-181 are highly enriched in skeletal muscle and play a key role in skeletal muscle metabolism [28, 29, 30, 31]. [score:1]
The top nine most abundant miRNAs shared between the two groups were ssc-miR-10b, ssc-miR-22-3p, ssc-miR-486, ssc-miR-26a, ssc-miR-27b-3p, ssc-miR-191, ssc-miR-378, ssc-126-5p and ssc-miR-181. [score:1]
In our sequencing libraries, five of these known myomiRs (miR-486, miR-26a, miR-27b, miR-378 and miR-181) were identified with the greatest abundance, accounting for 26% and 29% of the total normalized miRNA reads in the LPS-challenged and saline -treated groups, respectively. [score:1]
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Increasing evidence has indicated the diagnostic value and clinical implications of several miRNAs in heart diseases, such as miR-433, miR-21, miR-378, and miR-940 [19– 21]. [score:3]
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66
[+] score: 3
Overexpression of mir-378a or miR-376c significantly enhanced proliferation, migration and invasion of the extravillous trophoblast (EVT)-like cell line HTR8/SVneo, and both mimetics promoted outgrowth of primary EVT from placental explants 37, 38. [score:3]
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67
[+] score: 3
Pan B Toms D Shen W Li J MicroRNA-378 regulates oocyte maturation via the suppression of aromatase in porcine cumulus cellsAm. [score:3]
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68
[+] score: 3
miRDeep2miRExpressmiRNAKey miRNA Name FC (log2) p-Value miRNA Name FC (log2) p-Value miRNA Name FC (log2) p-Value mmu-miR-133a-3p −2.49 0.028 mmu-miR-1a-3p −3.01 0.028 mmu-miR-378-3p −2.65 0.028Results were filtered at corrected p-value < 0.05. [score:3]
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69
[+] score: 3
A closer look at those 5 miRNA revealed that the expression of 4 miRNA including mmu-miR-291a-5p, mmu-miR-291b-5p, mmu-miR-664-3p, and mmu-miR-1306-3p increased in tumor tissues following cigarette smoke exposure, yet they decreased in the parenchyma of exposed mice, whereas mmu-miR-378-3p displayed the same behavior in both tissues following MS exposure. [score:3]
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70
[+] score: 2
In addition to miR-33a/b, miR-122, miR-370, miR-335, miR-378/378*, miR-27 and miR-125a-5p have been implicated in regulating cholesterol homeostasis, fatty acid metabolism and lipogenesis [9]. [score:2]
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71
[+] score: 2
Thus, while seq_96718_x14 may be a mir-378 family member, it is distinct from miR-378-3p and not merely a single nucleotide variant occurring from the same locus. [score:1]
Interestingly, the mature sequence of one novel miRNA candidate, seq_96718_x14, is nearly identical to miR-378-3p (one nucleotide difference), but alignment of the precursor sequence mapped seq_96718_x14 to chromosome 10 rather than to chromosome 18 on which miR-378 resides. [score:1]
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72
[+] score: 2
miR-378 also showed the greatest magnitude changes in relative serum levels (range: 1.4–12-fold) of the set of novel candidate miRNAs (although these fold changes are considerably less than those observed with the dystromiRs described earlier in the text). [score:1]
Aside from the established dystromiRs, the four most differentially abundant miRNAs were miR-22, miR-30a, miR-193b and miR-378 (Figure 2A). [score:1]
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73
[+] score: 2
Identification of resting and type I IFN-activated human NK cell miRNomes reveals microRNA-378 and microRNA-30e as negative regulators of NK cell cytotoxicity. [score:2]
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74
[+] score: 2
We selected 14 of these miRs which might have been involved in regulation of angiogenesis, including miR-17-5p, miR-19a, miR-23a, miR-24, miR-31, miR-34a, miR-126, miR-130a, miR-132, miR-16, miR-21, miR-217, miR-221, and miR-378 for our study. [score:2]
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75
[+] score: 2
Other miRNAs from this paper: mmu-mir-16-1, mmu-mir-16-2, mmu-mir-378b, mmu-mir-378c, mmu-mir-378d
Tumor -induced miRNA16 and miRNA378 secretion changes as regulators and biomarkers of osteolytic bone metastasis [30]. [score:2]
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76
[+] score: 2
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-22, hsa-mir-29a, hsa-mir-30a, hsa-mir-29b-1, hsa-mir-29b-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-127, mmu-mir-132, mmu-mir-133a-1, mmu-mir-136, mmu-mir-144, mmu-mir-146a, mmu-mir-152, mmu-mir-155, mmu-mir-10b, mmu-mir-185, mmu-mir-190a, mmu-mir-193a, mmu-mir-203, mmu-mir-206, hsa-mir-148a, mmu-mir-143, hsa-mir-10b, hsa-mir-34a, hsa-mir-203a, hsa-mir-215, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-143, hsa-mir-144, hsa-mir-152, hsa-mir-127, hsa-mir-136, hsa-mir-146a, hsa-mir-185, hsa-mir-190a, hsa-mir-193a, hsa-mir-206, mmu-mir-148a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-22, mmu-mir-29a, mmu-mir-29c, mmu-mir-34a, mmu-mir-337, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-155, mmu-mir-29b-2, hsa-mir-29c, hsa-mir-34b, hsa-mir-34c, hsa-mir-378a, hsa-mir-337, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-215, mmu-mir-411, mmu-mir-434, hsa-mir-486-1, hsa-mir-146b, hsa-mir-193b, mmu-mir-486a, mmu-mir-540, hsa-mir-92b, hsa-mir-411, hsa-mir-378d-2, mmu-mir-146b, mmu-mir-193b, mmu-mir-92b, mmu-mir-872, mmu-mir-1b, mmu-mir-3071, mmu-mir-486b, hsa-mir-378b, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, mmu-mir-378b, hsa-mir-203b, mmu-mir-3544, hsa-mir-378j, mmu-mir-133c, mmu-let-7j, mmu-mir-378c, mmu-mir-378d, mmu-let-7k, hsa-mir-486-2
Finally, myogenic factor MyoD negatively regulates myogenic repressor MyoR via miR-378 during myoblast differentiation [23]. [score:2]
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During myogenic differentiation, MyoD directly increases production of miR-378, which enhances MyoD activity by repressing the anti-myogenic protein MyoR [42]. [score:2]
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78
[+] score: 1
Other miRNAs from this paper: mmu-mir-378b, mmu-mir-378c, mmu-mir-378d
Ergosterol peroxide Isolated from Ganoderma lucidum abolishes MicroRNA miR-378-Mediated tumor cells on chemoresistance. [score:1]
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79
[+] score: 1
Our previous study found that miR-196a, miR-486-5p, miR-664-star, and miR-378-star were significantly increased whereas miR-10a, miR-708, and miR-3197 were decreased in old hBM-MSCs. [score:1]
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80
[+] score: 1
Redova M Poprach A Nekvindova J Iliev R Radova L Lakomy R Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinomaJ Transl Med. [score:1]
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81
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For example, miR-27b was identified as a pro-angiogenic miRNA [25], and miR-378 is involved in tumor angiogenesis [28]. [score:1]
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82
[+] score: 1
Numerous miRNAs from this list were previously found altered in cancer, such as hsa-let-7e-3p, hsa-miR-4448, hsa-miR-223-3p, hsa-miR-3151-5p, hsa-miR-940, hsa-miR-378a-3p and hsa-miR-146a-5p. [score:1]
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83
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These authors also observed a correlation with abundance of miR-378 and muscle mass. [score:1]
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84
[+] score: 1
Furthermore, Brian E et al. reported that elevated serum miR-16, miR-378, and sICAM1 levels correlate with bone metastasis [13]. [score:1]
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85
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It is reported that exosomes contain plenty of miRs, including pro-angiomiRs (miR-21, miR-126, miR-130a, miR-132, miR-210, miR-378 and let-7f, etc. ) [score:1]
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86
[+] score: 1
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-27a, hsa-mir-29a, hsa-mir-101-1, dme-mir-1, dme-mir-2a-1, dme-mir-2a-2, dme-mir-2b-1, dme-mir-2b-2, dme-mir-10, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-101a, mmu-mir-124-3, mmu-mir-126a, mmu-mir-133a-1, mmu-mir-137, mmu-mir-140, mmu-mir-142a, mmu-mir-155, mmu-mir-10b, mmu-mir-183, mmu-mir-193a, mmu-mir-203, mmu-mir-143, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-183, hsa-mir-199b, hsa-mir-203a, hsa-mir-210, hsa-mir-222, hsa-mir-223, dme-mir-133, dme-mir-34, dme-mir-124, dme-mir-79, dme-mir-210, dme-mir-87, mmu-mir-295, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, dme-let-7, dme-mir-307a, dme-mir-2c, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-137, hsa-mir-140, hsa-mir-142, hsa-mir-143, hsa-mir-126, hsa-mir-193a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-29a, mmu-mir-27a, mmu-mir-34a, mmu-mir-101b, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-155, mmu-mir-10a, mmu-mir-210, mmu-mir-223, mmu-mir-222, mmu-mir-199b, mmu-mir-124-1, mmu-mir-124-2, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-378a, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-411, hsa-mir-193b, hsa-mir-411, mmu-mir-193b, hsa-mir-944, dme-mir-193, dme-mir-137, dme-mir-994, mmu-mir-1b, mmu-mir-101c, hsa-mir-203b, mmu-mir-133c, mmu-let-7j, mmu-let-7k, mmu-mir-126b, mmu-mir-142b, mmu-mir-124b
of 5′-isomiR reads Arm abundance hsa-miR-203 GAAAUGU 3p 8 8,774,451 45.5 hsa-miR-140 CCACAGG 3p 37 1,072,944 39.5 hsa-miR-126 GUACCGU 3p 54 776,502 13.8 hsa-miR-199b ACAGUAG 3p 55 724,009 27.0 hsa-miR-101 UACAGUA 3p 57 662,855 27.3 hsa-miR-10a CCCUGUA 5p 59 661,921 22.7 hsa-miR-143 UGAGAUG 3p 69 619,911 1.8 hsa-miR-378a UGGACUU 3p 71 402,197 6.0 hsa-miR-29a UAGCACC 3p 77 334,605 18.1 hsa-let-7a AGGUAGU 5p 89 269,329 0.6 The arm abundance of a 5′-isomiR is the percentage of all reads mapped to one arm that represents the 5′-isomiR. [score:1]
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