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42 publications mentioning hsa-mir-432

Open access articles that are associated with the species Homo sapiens and mention the gene name mir-432. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 401
As expected, western blotting showed that LRP6, TRIM29, and Pygo2 expression in both QGY-7703 and HepG2 cells were dramatically downregulated in response to miR-432 transfection, and upregulated by the miR-432 inhibitor (Figure 5D). [score:11]
Herein, we demonstrate that miR-432 simultaneously suppresses three important component of the wnt pathway, i. e. LRP6, TRIM29, and Pygo2 expression by directly targeting their 3′UTRs and that β-catenin nuclear accumulation could be robustly repressed by miR-432 overexpression in HCC. [score:10]
Interestingly, we also found that mir-432 expression was markedly downregulated in HCC cells and tissues and overexpression of miR-432 inhibited the proliferation and tumorigenicity of HCC cells in vitro and in vivo. [score:10]
MiR-432 upregulation drastically suppress HCC cell proliferation by inhibiting the expression of three key regulators of the Wnt/β-catenin signaling pathway, i. e. LRP6, TRIM29, and Pygo2. [score:10]
Furthermore, we demonstrated that miR-432 attenuated the activity of Wnt/β-catenin signaling, from plasma membrane to nucleus levels, by suppressing the expression of LRP6, TRIM29, and Pygo2 in HCC, which suggested that miR-432 acts as a tumor suppressor, and may represent an important target for clinical intervention in HCC by controlling Wnt/β-catenin signaling. [score:9]
Furthermore, we demonstrated that miR-432 attenuated the activity of Wnt/β-catenin signaling by suppressing the expression of LRP6, TRIM29, and Pygo2 in HCC, which suggesting that miR-432 act as a tumor suppressor and may represent a new target for clinical intervention of HCC by controlling Wnt/β-catenin signaling. [score:9]
IHC staining showing that miR-432 downregulation increased the percentages of Ki-67 positive cells, whereas miR-432 overexpression inhibited the percentages of Ki-67 positive cells. [score:8]
Collectively, our results suggested that miR-432 upregulation inhibits HCC cell proliferative capacity in vitro through regulation of G1/S transition. [score:7]
Supplemental Figure 2 illustrates that the mRNA level of β-catenin downstream targets, including Cyclin D1, MYC, TCF4 and LEF1, were significantly decreased in miR-432 -overexpressing cells, whereas their mRNA levels were increased in cells transfected with the miR-432 inhibitor. [score:7]
Furthermore, cellular fractionation showed that miR-432 overexpression inhibit nuclear accumulation of β-catenin (Figure 5B), indicating that miR-432 deactivates Wnt/β-catenin pathway by inhibiting β-catenin nuclear accumulation. [score:7]
To explore the mechanism underlying the suppressive effect of miR-432 on Wnt/β-catenin signaling, we used publicly available algorithms (TargetScan and miRanda) to predict the potential targets of miR-432 in humans. [score:7]
Clinical relevance of miR-432 downregulation and β-catenin nuclear accumulation, and the expression of LRP6, TRIM29 and Pygo2 in HCC. [score:6]
Importantly, the anchorage-independent growth ability of QGY-7703 and HepG2 cells was drastically repressed upon miR-432 overexpression cells, as indicated by the reduction in colony number and colony size on soft agar (Figure 2C), suggesting that miR-432 upregulation decreased the tumorigenicity of HCC cells in vitro. [score:6]
Consistent with the oncogenic effects of LRP6, TRIM29, and Pygo2 in HCC, miR-432 is downregulated in HCC, and its suppression dramatically promoted HCC cell proliferation both in vitro and in vivo. [score:6]
The above mentioned miR-432 targets are closely correlated with Wnt/β-catenin signaling pathway, therefore, we further examined the effect of miR-432 deregulation on the expression of downstream genes of the Wnt/β-catenin signaling pathway. [score:6]
The relative expression of miR-432 in tumors were quantified by real-time PCR, which determined by comparing the miR-432 expression in N1 (i. e. the expression of miR-432 was considered as 1.0). [score:6]
However, there are other studies showed that miR-432 was amplified in metastatic melanoma and upregulation of miR-432 markedly enhanced the tumorigenicity in vivo by modulating ADAR1 expression [28]. [score:6]
MiR-432 expression is markedly downregulated in HCC cells and clinical tissues. [score:5]
The expression of miR-432 was defined based on the threshold cycle (Ct), and relative expression levels were calculated as 2 [−[(Ct of miR-432) − (Ct of U6)]] after normalization with reference to the quantification of U6 small nuclear RNA expression. [score:5]
Our current study shows that miR-432 simultaneously represses the expression of three important factors of β-catenin pathway: LRP6, TRIM29, and Pygo2, which subsequently suppresses β-catenin activation in HCC. [score:5]
Consistent with the overexpression results, MTT and colony formation assays showed that miR-432 suppression dramatically increased the growth rate of both miR-432 overexpression cells compared with that of control cells transfected with negative control (NC) (Supplemental Figure 1, Figure 3A and 3B). [score:5]
Inhibiting miR-432 expression enhanced HCC cell proliferation. [score:5]
MiR-432 was downregulated in multiple tumors, for instance, ovarian cancer, cervical cancer, human pituitary GH adenomas, and plays a role as tumor suppressor gene by different mechanism [24- 26]. [score:5]
Taken together, our results represent a novel mechanism that, from plasma membrane to nucleus, miR-432 suppressed the β-catenin pathway activation by repressed the expression of LRP6, TRIM29, and Pygo2 in HCC, and a functionally and clinically relevant epigenetic mechanism of HCC pathogenesis. [score:5]
To examine the effect of LRP6, TRIM29, and Pygo2 suppression on the proliferative capacity of the miR-432 inhibitor in HCC cells, we studied the effects of their depletion using specific siRNAs. [score:5]
Expression profiling of miRNAs showing that miR-432 is downregulated in HCC tissues (T) compared with matched non-cancerous liver tissue (N) (n = 89, p<0.001; NCBI /GEO /GSE 36915). [score:5]
Ectopic expression of miR-432 inhibited HCC cell proliferation. [score:5]
Clinical relevance of miR-432, β-catenin nuclear accumulation and expression of its targets in HCC. [score:5]
MiR-432 inhibition promoted HCC cell proliferation in vitroWe further examined the effect of miR-432 inhibition on HCC cell proliferation. [score:5]
MTT assay revealed that miR-432 upregulation suppresses QGY-7703 and HepG2 stable cell lines at indicated times after seeding. [score:5]
Ectopic expression of miR-432 inhibited, whereas repression of endogenous miR-432 promoted the proliferation and tumorigenicity of HCC cells in vitro and in vivo. [score:5]
MiR-432 mimic and miR-432 inhibitor (a cholesterol-conjugated 2′-O-Me modified antisense oligonucleotide designed specifically to bind to and inhibit endogenous miR-432 molecule) were synthesized and purified by RiboBio (Guangzhou, Guangdong). [score:5]
Individually silencing of LRP6, TRIM29 or Pygo2 decreased the transcriptional activity of the downstream effectors TCF and LEF in HCC cells whose miR-432 expression was suppressed (Figure 5F). [score:5]
As shown in Figure 5A, miR-432 overexpression markedly decreased the luciferase activity of TOPflash or FOPflash reporter; conversely, transfection of miR-432 inhibitor increased the luciferase activity of TOPflash or FOPflash reporter, compare with vector or negative control, respectively. [score:5]
Collectively, these results support the notion that miR-432 downregulation promotes proliferation in HCC and activates the Wnt/β-catenin signaling pathway by repressing multiple important regulator this pathway. [score:5]
Taken together, our results suggest that miR-432 overexpression inhibits the Wnt/β-catenin signaling pathway. [score:5]
The expression of the miRNA was defined based on Ct, and relative expression levels were calculated as 2 [−[(Ct of miR-432) − (Ct of U6)]] after normalization with reference to the expression of small nuclear RNA U6. [score:5]
Using 10 freshly collected clinical HCC samples, we found that miR-432 expression was inversely correlated with the expression of β-catenin(r = −0.688, P = 0.002), LRP6 (r = −0.872, P = 0.007), TRIM29 (r = −0.775, P = 0.004), Pygo2 (r = −0.663, P = 0.014) (Figure 6A and 6B). [score:5]
Herein, we report that miR-432 deactivates the Wnt/β-catenin pathway by simultaneously suppressing the expression of LRP6, TRIM29, and Pygo2, and consequently repress proliferation in HCC. [score:5]
Taken together, these results suggest that miR-432 downregulation promotes the proliferation of HCC cells in vitro. [score:4]
MiR-432 downregulation contributed to HCC progression in vivoTo investigate whether miR-432 inhibits HCC progression in vivo, we used a xenografted tumor mo del to examine the biological effect of miR-432. [score:4]
Consistent with previous studies, our studies demonstrate an important role of miR-432 in modulating tumor development and may represent a promising therapeutic target in HCC. [score:4]
These results suggest that LRP6, TRIM29, and Pygo2 are essential for miR-432 downregulation -mediated HCC cell proliferation. [score:4]
Altered nuclear translocation of β-catenin in response to deregulated miR-432 expression. [score:4]
These results demonstrated that miR-432 suppressed LRP6, TRIM29, and Pygo2 directly in HCC cells. [score:4]
MiR-432 overexpression inhibited the Wnt/β-catenin signaling pathway. [score:4]
Collectively, these results indicated that miR-432 is downregulated in HCC. [score:4]
A newly study reveal that miR-432 induced neurite projections, arrested cells in G0–G1, reduced cell proliferation and could significantly repress the expression of NESTIN/NES, RCOR1/COREST and MECP2,which suggest that miR-432 may play an important role in regulating neuronal differentiation of human neuroblastoma cells [27]. [score:4]
LRP6, TRIM29 and Pygo2 are direct targets of miR-432. [score:4]
gov/, n=48 pairs) in liver hepatocellular carcinoma and matched non-cancerous liver tissue and found that miR-432 was significantly downregulated in tumor samples (Figure 1B). [score:4]
However, a miR-432 mutant containing three altered nucleotides in the seed sequence showed no inhibitory effect on luciferase activity. [score:3]
MiR-432 is downregulated in HCC. [score:3]
Finally, we examine whether miR-432 -mediated suppression of LRP6, TRIM29, and Pygo2 and β-catenin nuclear accumulation in HCC are clinically relevant. [score:3]
Furthermore, IHC analysis revealed that miR-432-silenced tumors showed higher percentages of Ki-67 -positive cells, whereas miR-432 -overexpressing tumors displayed lower percentages of Ki-67 positive cells than the control tumors (Figure 4D). [score:3]
Real-time PCR analysis of miR-432 expression in primary HCC tissues (T) with matched adjacent non-tumor tissues (ANT) from eight individual patients. [score:3]
Expression profiling of miR-432 from The Cancer Genome Altas (TCGA) datasets in liver hepatocellular carcinoma ((http://cancergenome. [score:3]
Real-time PCR analysis of miR-432 expression in normal human LO2 hepatocyte and in HCC cell lines (Hep3B, MHCC97L, Huh7, HCCC-9810, HepG2, BEL-7402, MHCC97H and QGY-7703). [score:3]
MiR-432 suppressed LRP6, TRIM29, and Pygo2 directly. [score:3]
MiR-432 downregulation contributed to HCC progression in vivo. [score:3]
of pGL3- LRP6-3′UTR, pGL3- TRIM29-3′UTR and pGL3- Pygo2-3′UTR reporter cotransfected with miR-432, miR-432 -inhibitor and miR-432-mut oligonucleotides in HCC cells. [score:3]
By contrast, transfection with the miR-432 inhibitor increased the luciferase activities. [score:3]
By analyzing a published microarray -based high-throughput assessment, miR-432 was identified to be significantly downregulated in HCC tissues compared with non-cancerous liver tissue (n = 89; P < 0.05; NCBI/GEO/GSE36915; Figure 1A). [score:3]
Furthermore, we found that transfection of miR-432 inhibitor drastically increased the percentage of cells in the S peak but decreased that in the G0/G1 peak (Figure 3D and 3E). [score:3]
Suppression of LRP6, TRIM29, and Pygo2 is functionally important for the biological effects of miR-432 in HCC. [score:3]
We further examined the effect of miR-432 inhibition on HCC cell proliferation. [score:3]
As shown in Figure 5E, ectopic expression of miR-432 decreased the luciferase activities of the 3′UTRs of LRP6, TRIM29, and Pygo2. [score:3]
In summary, the present study demonstrated the tumor-suppressive effect of miR-432 in HCC. [score:3]
In addition, the anchorage-independent growth ability of QGY-7703 and HepG2 HCC cells was significantly increased in response to miR-432 inhibitor (Figure 3C). [score:3]
Thus, the above findings suggest that miR-432 expression and its biological functions might be tumor-type dependent. [score:3]
Correlation between miR-432 and β-catenin LRP6, TRIM29 and Pygo2 expression was analyzed by SPSS software. [score:3]
As shown in Figure 2A and 2B, upregulation of miR-432 significantly decreased the growth rate of QGY-7703 and HepG2 cells, analyzed by MTT and colony formation assays. [score:3]
Predicted miR-432 target sequences in the 3′UTRs of LRP6, TRIM29 and Pygo2. [score:3]
Collectively, these results demonstrate that miR-432 finctions as a tumor suppressor in HCC in vivo. [score:3]
To generate a mir-432 expression vector, approximately 250-bp genomic fragment up and downstream of the pre-mir-432 form was generated by PCR amplification from genomic DNA, and subcloned into the EcoRI and SpeI sites of the pSin-EF2-puro retroviral vector (Clontech Laboratories Inc. [score:3]
We further performed luciferase reporter assay to confirm whether LRP6, TRIM29, and Pygo2 are direct targets of miR-432. [score:3]
MiR-432 is downregulated in HCC cell lines and tissues. [score:3]
Strikingly, real-time PCR showed that miR-432 was downregulated in all 10 tumor tissue samples and in eight HCC cell lines (QGY-7703, Huh7, MHCC97L, Hep3B, HepG2, BEL-7402, MHCC97H, HCCC-9810)compared with adjacent non-cancerous tissues and normal human LO2 hepatocyte, respectively (Figure 1C and 1D). [score:3]
Figure 5C shows that three critical components of the Wnt/β-catenin signal pathway, including LRP6, TRIM29, and Pygo2, are potential targets of miR-432. [score:3]
of indicated HCC cells stably expressing miR-432 or Vector. [score:3]
Similarly, flow cytometry showed that miR-432 overexpression decreased the percentage of HCC cells in S phase and significantly increased the percentage of cells in G1/G0 (Figure 2E). [score:3]
The correlation analysis between β-catenin /p84, LRP6/α-tubulin, or TRIM29/α-tubulin, or Pygo2/α-tubulin ratio with miR-432 expression was performed by Student's 2-tailed t-test. [score:3]
MiR-432 inhibition promoted HCC cell proliferation in vitro. [score:2]
The clinical significance and mechanism of miR-432 downregulation in HCC require further investigation. [score:2]
Analysis of miR-432 expression in HCC tissues compared with that in matched noncancerous hepatic tissues was using a published microarray -based high-throughput assessment (n = 89; P < 0.05; NCBI/GEO/GSE36915). [score:2]
Therefore, we detect the effect of miR-432 in regulating the wnt/β-catenin signaling. [score:2]
MTT analysis of the proliferation ability of HCC cells transfected with miR-432-in or NC. [score:1]
Herein we provide evidence for a novel mechanistic link between miR-432 and the oncogenic Wnt/β-catenin activity in HCC. [score:1]
Furthermore, BrdU incorporation assay showed that the percentage of cells in S phase was dramatically decreased in miR-432 -overexpressing HCC cells compared with the control cells (Figure 2D). [score:1]
Representative micrographs (left) and quantification of BrdU positive signaling in the cells transfected with miR-432 or Vector. [score:1]
As shown in Figure 4A-4C, the tumors formed by miR-432-silenced cells were larger in both size and weight than the tumors formed by control cells. [score:1]
The miR-432 mutant (miR-432-mut) contained three altered nucleotides in the seed sequence. [score:1]
One group of mice was inoculated subcutaneously with HepG2/Vector cells (5× 10 [6]) in the left dorsal flank and with HepG2/mir-432 cells (5× 10 [6]) in the right abdomen flank per mouse. [score:1]
Conversely, the tumors formed by miR-432-transduced-HCC cells were smaller and lighter than the control tumors. [score:1]
of indicated HCC cells transfected with miR-432-in or NC. [score:1]
To investigate whether miR-432 inhibits HCC progression in vivo, we used a xenografted tumor mo del to examine the biological effect of miR-432. [score:1]
To determine the effect of miR-432 on HCC progression, QGY-7703 and HepG2 cells were selected for further study (Supplemental Figure 1). [score:1]
The expression level of miR-432 was performed using miR-432-specific primer and probe (TaqMan MicroRNA Assay Kit, Applied Biosystems, Foster City, CA) on an ABI 7900 system (Applied Biosystems). [score:1]
Expression of miR-432 and β-catenin nuclear accumulation(p84 served as loading control), LRP6, TRIM29 and Pygo2 protein, as measured by real-time PCR (top) and western blotting (bottom), respectively. [score:1]
Representative micrographs (left) and quantification of BrdU positive signaling in the cells transfected with miR-432-in or NC. [score:1]
pSin-EF2-miR-432 and pSin-EF2-NC were co -transfected with the PMD2g and PSPAX packaging plasmid into 293FT cells using the standard calcium phosphate transfection method. [score:1]
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[+] score: 357
As expected, Western blotting demonstrated that E2F3 and AXL expression in both A549 and H1299 cells were dramatically downregulated in response to miR-432 mimics transfection, but upregulated by the transfection of miR-432 inhibitor (Figure 3C and 3D). [score:11]
In previous study, miR-432 was reported to act as a tumor suppressor and its downregulation in multiple tumors, for instance, ovarian cancer, cervical cancer, Hepatocellular carcinoma and pituitary GH adenomas, promotes tumorigenesis and progression through modulating different targeted genes [6– 8, 20]. [score:8]
All of these results support that miR-432 suppresses E2F3 and AXL expression by directly targeting their 3′UTR in LAD cells. [score:8]
To explore the mechanism underlying the tumor suppressive role of miR-432 on LAD, we used publicly available algorithms (TargetScan and miRanda) to predict the potential targets of miR-432 in humans. [score:7]
Importantly, our results demonstrated that, in the absence or presence of cisplatin, when miR-432 -expressing cells re-expressed E2F3 or AXL, their reduction of cell vitality were reversed, whereas silencing E2F3 or AXL could attenuate the effects of miR-432 inhibition on cell vitality. [score:7]
As expected, in contrast to the vehicle at 0 h timepoint, the data showed that cisplatin could up-regulate the expression of miR-432 (Figure 4E and 4F). [score:6]
Thus, it was concluded that down-regulation of E2F3 may be a molecular mechanism by which miR-432 exerted its functions as a tumor suppressor in human LAD cells. [score:6]
Furtherrmore, miR-432 overexpression could sensitize LAD cells to cisplatin treatment, Of note, E2F3 and AXL were identified as the direct targets of miR-432 to fully fucntions in LAD. [score:6]
In this study, we found that miR-432 is significantly suppressed in LAD tissues and its expression levels are inversely correlated with clinical tumor stage and predict poor prognosis in LAD patients. [score:5]
For example, miR-432 suppresses ADAR1 expression and promotes cell proliferation in metastatic melanoma. [score:5]
The results showed that miR-432 inhibitor rather than the inhibitor control enhanced cell vitality in both A549 and H1299 cells (Figure 2D). [score:5]
The relationship between the miR-432 expression levels and clinic-pathological variables are summarized in Table 1. Of note, reduced miR-432 expression was observed to be significantly associated with advanced clinical tumor stage (p = 0.030, Table 1), but not with patients' age, gender and lymphatic metastasis. [score:5]
To investigate whether miR-432 inhibits the proliferation of tumor cells in vivo, we applied a retrovirally overexpression strategy to examine whether miR-432 could inhibit tumorigenesis in xenografted tumor mo del. [score:5]
Up-regulation of miR-432 enhances the sensitivity of A549 and H1299 cells to cisplatin in vitro Previous research demonstrated that miRNA dysregulation is related to the chemoresistance of cancers, including lung cancer [17, 18]. [score:5]
Inhibitor control + Cisplatin vs miR-432 inhibitor + Cisplatin:* p < 0.05; ** p < 0.01. [score:5]
Alternatively, miR-432 induces tumor suppression in hepatocellular carcinoma cells by targeting LRP6, TRIM29 and Pygo2, which subsequently deactivates Wnt/β-catenin signaling pathway. [score:5]
In addition, depletion of E2F3 and AXL dramatically suppressed the increased proliferaion of miR-432–inhibited E2F3 and AXL cells (Figure 5C and 5D). [score:5]
Importantly, when E2F3 and AXL was ectopically overexpressed in miR-432 mimics–transduced A549 and H1299 cells (Figure 5A and 5B), the inhibition of cell vitality induced by miR-432 mimics were, at least partly, antagonized. [score:5]
A549 (C) and H1299 (D) cells transfected with miR-432 mimics or miR-432 inhibitors, and the expression levels of E2F3(left) and AXL(right) were detected by Western blotting. [score:5]
Therefore, to validate it, we treated inhibitor control- or miR-432 inhibitor -transfected A549 and H1299 cells with cisplatin (5 μg/ml) for different timepoints. [score:5]
However, the expression and function of miR-432 in LAD, as well as and its putative target genes, was unclear to date. [score:5]
The median value of all cases was chosen as the cutoff point for separating miR-432 high -expression cases from miR-432 low -expression cases [12]. [score:5]
In contrast, suppression of miR-432 by transfection with its inhibitor showed the opposite tendency (Figure 2F). [score:5]
Similarly, our in vitro and in vivo studies demonstrated that after overexpression of miR-432, the lung cancer cells displayed decrease of cell growth and tumor formation, further validating miR-432 as a tumor suppressor gene in LAD. [score:5]
We next determined whether there was any association between the expression levels of miR-432 and its targets in human LAD tissues. [score:5]
In conclusion, our work demonstrated miR-432 plays a tumor-suppressive role in LAD and its function is mainly mediated by its targets, E2F3 and AXL. [score:5]
In this study, we show that the expression of miR-432 was markedly reduced in LAD tissues and its expression was associated with clinical tumor stage. [score:5]
E2F3 and AXL are the direct targets of miR-432 in LAD cells. [score:4]
Up-regulation of miR-432 enhances the sensitivity of A549 and H1299 cells to cisplatin in vitro. [score:4]
Functionally and mechanistically, our in vitro and in vivo assays indicate that miR-432 overexpression could inhibite the cell proliferation and tumor formation of LAD. [score:4]
Although the basal levels of AXL and E2F3 are different in A549 and H1299, the regulation of miR-432 mimics/inhibitor towards drug resistance in these two cell lines looks the same (Figure 4A, 4B and 4I). [score:4]
Previous study showed that miRNA dysregulation can alter cisplatin chemoresistance in cancer cells [25] and, of note, suppression of E2F3 is a potential mechanism by which miR-200b reverses chemoresistance of docetaxel-resistant LAD cells [26], suggesting that miR-432 may have a similar function about drug resistance in lung cancer. [score:4]
As expected, ectopic expression of miR-432 significantly decreased the growth rates of A549 and H1299 cells, analyzed bys (Figure 2B), and whereas overexpression of the miR -mimics control failed to influence cell vitality compared with non -transfected cells. [score:4]
Bars indicate s. d. (D) Patients with high levels of miR-432 expression showed increased survival times compared with patients with low levels of miR-432 expression. [score:4]
Herein, our data showed that E2F3 was also a direct target of miR-432 in LAD. [score:4]
However, after withdrawal of aphidicolin, overexpression of miR-432 led to a significant accumulation in the S phase of A549 and H1299 cells (Figure 2G), indicating the anti-proliferation effect of miR-432 was achieved partly by regulating the cell cycles in LAD. [score:4]
Figure 2Effect of miR-432 on tumorigenesis in vitro and in vivo (A) miR-432 expression in A549 and H129 cells was determined by RT—qPCR at 24, 48 and 72 h after transfection with miR-432 mimics or the negative control. [score:3]
However, miR-423 also function as an oncogene in melanoma to promote metastasis through its targeted gene, ADAR1, further surporting the existence of a tumor type-specific manner of miR-432 during functions. [score:3]
On the contrary, the increase of cell vitality caused by miR-432 inhibitor was attenunated by silencing AXL (Figure 5G) and E2F3 (Figure 5H). [score:3]
To further illustrate the co-participation of miR-432, AXL and E2F3 during LAD progression, we evaluated their expression in LAD tissues and showed that miR-432 was inversely correlated with the expression levels of E2F3 and AXL. [score:3]
Of interest, the expression level of miR-432 increased with cisplatin exposure in a dose-and time -dependent manner (Figure 4E and 4F). [score:3]
Then, as E2F3 and AXL have been reported to function as oncogene to promote cell proliferation and drug resistance in various tumors [15, 16], and taken the potential tumor suppressor role of miR-432 in LAD based on the above results together, E2F3 and AXL were selected for the detailed study. [score:3]
Suppression of E2F3 and AXL is functionally important for the biological effects of miR-432 in LAD. [score:3]
However, transfection of miR-432 inhibitor in H1299 led to the increased activities of the 3′UTRs of E2F3 and AXL (Figure 3I and 3J). [score:3]
Transfection of miR-432 mimics resulted in significant overexpression of miR-432 (Figure 2A). [score:3]
When clinic-pathological predictors were included, multivariate analysis reveals that miR-432 expression levels remains significant as independent predictors for recurrence-free survivals. [score:3]
Figure 3(A and B) Predicted miR-432 target sequences in the 3′UTRs of E2F3 and AXL (W). [score:3]
Figure 3A and 3B shows the two potential targets of miR-432, including E2F3 and AXL. [score:3]
Interestingly, we also found that AXL is an additional target of miR-432, which may be the other possibility that decreased miR-432 causes abnormal proliferation and chemoresistance in LAD. [score:3]
Effects of cisplatin treatment at different concentrations and various time of on miR-432 expression in A549 (E) and H1299 (F). [score:3]
Totally, our findings highlight the importance of miR-432 dysfunction in promoting tumor progression and chemoresistance and implicate miR-432 as a potential therapeutic target in lung cancer. [score:3]
As shown in Figure 3E and 3F, ectopic expression of miR-432 decreased the luciferase activities of the 3′UTRs of E2F3 and AXL in HEK193T cells. [score:3]
However, a miR-432 mutant containing four altered nucleotides in the seed sequence showed no inhibitory effects on luciferase activity. [score:3]
However, miR-432 inhibition significantly attenuated the decrease of cell vitality in A549 and H1299 cells in response to cisplatin treatment (Figure 4A and 4B), which suggests that miR-432 may affect the sensitivity of cisplatin in LAD. [score:3]
We then performed in vitro loss-of-function analyses by antagonizing miR-432 with miR-432 inhibitor (Figure 2C). [score:3]
After co-transfection with miR-432 inhibitor or its control and WT/Mut 3′-UTR of E2F3 (I) and AXL (J) in H1299, the luciferase activity was detected. [score:3]
We further performed luciferase reporter assay to confirm whether E2F3 and AXL are direct targets of miR-432. [score:3]
Furthermore, the miR-432 expression decreased upon cisplatin treatment, but E2F3 and AXL showed the opposite tendency. [score:3]
Collectively, these results demonstrate that miR-432 functions as a tumor suppressor in LAD. [score:3]
MiR-432 suppresses E2F3 and AXL directly. [score:3]
Our results confirmed that miR-432 could also inhibit the cell vitality through arresting the cell cycle into S phase, although the mechanism needs to be validated. [score:3]
Lung cancer cells, A549, transfected with adenoviruses expressing miR-432-EGFP or its control, were harvested and resuspended in Matrigel/RPMI (1:1). [score:3]
Clinical relevance of miR-432 and its targets in LAD. [score:3]
The effects of silencing E2F3 and AXL on miR-432 inhibitor in A549 (C) and H1299 (D) cells were detected by MTS. [score:3]
In the presence of Cisplatin, the effects of over -expressing E2F3 or AXL on the miR-432 mimics transfected A549 (E) and H1299 (F) cells was detected by MTS. [score:3]
Relative miR-432 expression levels in LAD tissues and its clinical significance. [score:3]
The wild-type and mutants E2F3 3′-UTR and AXL 3′-UTR were generated on the miR-432 target recognition sites (seed sequences). [score:3]
As shown in Supplementary Figure S1A, the expression of miR-432 is relatively lower in A549 than in H1299. [score:3]
MiR-432 is downregulated in LAD. [score:3]
Indicated siRNA, vectors and miR-432 mimics/inhibitor transfections were carried out using Lipofectamine 2000 according to the manufacturer's protocol. [score:3]
These findings provide newinsight into the molecular pathogenesis of LAD and implicate miR-432 as apotential prognostic biomarker and therapeutic target of LAD. [score:3]
Clinical associations of miR-432 with E2F3 and AXL expression. [score:3]
Based on the basal level of miR-432 is relatively lower in A549 than in H1299 (Supplementary Figure S1A), we over-expressed miR-432 in A549. [score:3]
Therefore, we believe that deppressed miR-432 could promote the disease progression, expecially the drug resistence, though E2F3 and AXL. [score:3]
Also, Kaplan–Meier survival analyses showed that depressed miR-432 expression was correlated with cancer-specific death of LAD patients. [score:3]
These results suggest that the mechanism miR-432 functions in LAD is very comlex owing to its multiple targets, which needs to be validated in the long run. [score:3]
The cell vitality was assayed by MTS after over -expressing E2F3 or AXL in miR-432 mimics transfected A549 (A) and H1299 (B) cells. [score:2]
As expected, our results showed that miR-432 could regulate the sentivity of cancer cells to cisplatin treatment. [score:2]
Furthermore, DNA synthesis levels, as examined with the BrdU incorporation assay, were significantly decreased in miR-432 -overexpressing cells, whereas control cells had relatively higher BrdU incorporation rates (Figure 2E). [score:2]
Effects of miR-432 inhibitor transfection on the cisplatin sensitivity were assayed by MTS method in A549 (A) and H1299 (B). [score:2]
MiR-432 regulates cell proliferation of LAD in vitro and in vivo To determine the biological activity of miR-432 in LAD, A549 and H1299 were selected for further study. [score:2]
Also, miR-432 overexpression could significantly increase the Cisplatin -induced apoptosis of A549 or H1299 cells when compared the mimics control treated with cisplatin, as detected by FCM (Figure 4D). [score:2]
Figure 4Effects of miR-432 inhibitor transfection on the cisplatin sensitivity were assayed by MTS method in A549 (A) and H1299 (B). [score:2]
To verify the regulation miR-432 towards AXL and E2F3 in LAD, the basal levels of these parameters were firstly detected by RT-qPCR. [score:2]
These results further demonstrate that miR-432 could regulate the sensitivity of H1299 and A549 cells to cisplatin. [score:2]
Therefore, combining cisplatin with miR-432 regulation may serve as a potential approach for lung cancer therapy. [score:2]
Figure 5The cell vitality was assayed by MTS after over -expressing E2F3 or AXL in miR-432 mimics transfected A549 (A) and H1299 (B) cells. [score:2]
E2F3 and AXL are functional for miR-432 -mediated regulationof cell proliferation and drug sensitivity. [score:2]
HEK-293T cells were co -transfected with miR-432 mimics or mimics control with WT/Mut 3′-UTR of E2F3 (E) and AXL (F). [score:1]
It was found that miR-432 levels were negatively correlated with the levels of E2F3 and AXL (Figure 6A and 6B), which confirms the inter-connection between miR432 and E2F3 or AXL in the pathological progression in LAD. [score:1]
As miR-432 was reported to be related the drug resistance in ovarian cancer, we hypothesized that miR432 may be endowed with the same function in LAD. [score:1]
Then, we overexpressed miR-432 using its mimics to investigate its effect on the sensitivity of lung cancer cell lines A549 and H1299 to cisplastin. [score:1]
Recent study revealed that miR-432 reduced cell proliferation through arresting cells in G0-G1 in human neuroblastoma cells [21]. [score:1]
After adhesion, cells were transfected with miR-432 mimics or mimics control. [score:1]
To determine the biological activity of miR-432 in LAD, A549 and H1299 were selected for further study. [score:1]
Previous studies have reported that miR-432 was depressed in various tumors, such as hepatocellular carcinoma, cervical and ovarian cancer [6– 8]. [score:1]
Correlations between miR-432 expression and clinicopathological characteristics in lung adenocarcinoma patients. [score:1]
The cell vitality (C) and apoptotic fraction (D) were analyzed in A549 and H1299 cells after cisplatin treatment at various concentrations with or without miR-432 mimics transfection. [score:1]
All these results confirm the important involvement of E2F3 and AXL during miR-432 functions in LAD. [score:1]
The group of patients who had higher miR-432 levels had a less rate of mortality than patients who had not (p = 0.036, Figure 1D). [score:1]
As shown in Figure 2H and 2I, the tumors formed by miR-432 -mimics-transduced cells were smaller and lighter than the groups of mimics or untreated controls. [score:1]
The same experiments were performed to evaluate the effect of silencing E2F3 or AXL on cisplatin sensitivity in miR-432 inhibitor -transfected A549 (G) and H1299 (H) cells. [score:1]
The miR-432 mutant (M) contained four altered nucleotides in the seed sequence. [score:1]
Effect of miR-432 on tumorigenesis in vitro and in vivo. [score:1]
To confirm the relation between miR-432 and E2F3/AXL, we evaluated the expression levels of these parameters in A549 and H1299 cells. [score:1]
In this study, immunohistochemical analysis was performed to measure the protein levels of Ki-67 in the tumor tissues (Figure 1E) and a significant negative association was identified between Ki67 labeling index with miR-432 expression in LAD tissues (p = 0.016, Table 1). [score:1]
MiR-432 regulates cell proliferation of LAD in vitro and in vivo. [score:1]
The above data indicates the potential involvement of miR-432 in the pathological progression of LAD. [score:1]
To elucidate the role of miR-432 in lung cancer, we first analyzed its correlation with clinicopathologic parameters in patients with LAD. [score:1]
Cisplatin + mimics control vs Cispliatin + miR-432 mimics: * p < 0.05; ** p < 0.01. [score:1]
Correlations between miR-432 expression with clinicopathological parameters were evaluated by the Spearman's test. [score:1]
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3
[+] score: 240
This explains that the suppressive effect of miR-432 on JEV replication is specifically due to SOCS5 downregulation in miR-432 overexpressing cells and SOCS5 has a direct regulatory effect on anti-viral Jak-STAT pathway. [score:10]
The overexpression of miR-432 resulted into the suppression of SOCS5 expression that ultimately led to the enhanced STAT1 phosphorylation creating strong anti-viral milieu in the cell due to enhanced ISRE activity. [score:7]
This demonstrated that JEV downregulated miR-432 levels in mouse brain, which led SOCS5 upregulation. [score:7]
These findings support that JEV downregulates miR-432 in order to induce SOCS5 expression, to negatively regulate the Jak-STAT pathway to aid the replication and survival of the virus. [score:7]
JEV infection downregulates miR-432 levels and leads to SOCS5 upregulation. [score:7]
We demonstrated that JEV downregulates miR-432 in CHME3 cells, which leads to the increased expression of SOCS5. [score:6]
Overexpression of miR-432 led to the downregulation of SOCS5 and this resulted to enhanced phosphorylation of STAT1 post JEV infection (Fig. 3A). [score:6]
miR-432 overexpression enhances Jak-STAT signaling by downregulating SOCS5. [score:6]
The SOCS5 was downregulated upon miR-432 overexpression (Fig. 2A). [score:6]
JEV infection downregulates miR-432 expression. [score:6]
miR-432 overexpression suppress viral replication. [score:5]
Since SOCS5 is a potential target of miR-432, therefore the levels of SOCS5 expression was analysed post JEV infection. [score:5]
Data was considered significant when P < 0.05; *denotes P < 0.05, **denotes P < 0.01, ***denotes P < 0.001 How to cite this article: Sharma, N. et al. Japanese Encephalitis Virus exploits the microRNA-432 to regulate the expression of Suppressor of Cytokine Signaling (SOCS) 5. Sci. [score:5]
The increased expression of miR-432 suppressed SOCS5 levels and created strong anti-viral environment in the cell, which led the reduced viral replication. [score:5]
Graph shows downregulated levels of viral RNA in miR-432 overexpressing cells at both time points as compared to scramble transfected cells. [score:5]
miR-432 overexpression suppressed SOCS5 levels causing enhanced Y-701 STAT1 phosphorylation. [score:5]
Since SOCS5 inhibits auto-phosphorylation of Jaks, the effect of miR-432 overexpression was analysed on Jak-STAT signalling. [score:5]
To confirm the targeting of SOCS5 UTR by miR-432, mimic sequence of miR-432 was overexpressed in CHME3 cells along with scramble control. [score:5]
For validation of SOCS5 UTR as target of miR-432, 100 pmol of miR-432 mimic was overexpressed in CHME3 cells. [score:5]
The viral RNA titre was found to be lower in miR-432 overexpressing cells which indicated that miR-432 suppressed the viral replication (Fig. 4A). [score:5]
The expression of miR-432 was normalized by RNU24 expression as endogenous control. [score:5]
To further delineate the effect of miR-432 on SOCS5, antimiR-432 was overexpressed in CHME3 cells, which resulted into increased levels of SOCS5 upon antimiR-432 overexpression (Fig. 2C). [score:5]
The validation of miR-432 downregulation upon JEV infection was also done in brain tissue of JEV infected mice in-vivo (Fig. 1B). [score:4]
SOCS5 is a negative regulator of Jak-STAT pathway 18 so the effect of miR-432 overexpression was analysed on Jak-STAT pathway. [score:4]
miR-432 downregulated SOCS5; which led to the enhanced phosphorylation of STAT1 and increased ISRE activity. [score:4]
miR-432 downregulates viral replication upon JEV infection. [score:4]
The miR-432 was found to be downregulated in CHME3 cells upon JEV infection (Fig. 1A). [score:4]
miR-432 upregulates STAT1 phosphorylation upon JEV infection. [score:4]
The mutated UTR clone did not display reduction in luciferase activity which confirmed the SOCS5 as a target of miR-432. [score:3]
miR-432 targets SOCS5. [score:3]
The enhanced luciferase activity was observed in miR-432 overexpressing cells post JEV infection (Fig. 3E). [score:3]
The effect of JEV on the expression pattern of miR-432 is time dependent. [score:3]
The decreased luciferase activity was observed due to targeting of SOCS5 3′UTR by miR-432 (Fig. 2D). [score:3]
For validation of microRNA targeting, 3′UTR clone of SOCS5 in pEZX-MT06 luciferase vector (#HmiT054032-MT06, GeneCopoeia) was transfected into HeLa cells along with miR-432 mimic or scramble mimic to observe the effect on luciferase activity. [score:3]
To further validate the targeting of 3′UTR of SOCS5 by miR-432 mimic, luciferase vector containing 3′UTR of SOCS5 was transfected along with miR-432 mimic. [score:3]
Hence, miR-432 overexpression created a potent antiviral milieu in the cell, which further led to the reduced viral replication in the cells as well as release of viral particles in culture supernatant. [score:3]
miR-432 overexpression reduced viral copies in supernatant at both time points. [score:3]
A mutant clone was generated deleting the targeting region present in SOCS5 UTR (shown in Fig. 2) and transfected along with miR-432 mimic. [score:3]
To further study the specificity of the targeting, the recognition sequences of miR-432 present in 3′UTR of SOCS5 were deleted and cloned in to luciferase vector. [score:3]
The increased levels of IL-6 and TNF-α were found in miR-432 overexpressing cells after JEV infection (Supplementary Fig. 3A,C). [score:3]
org were used to predict SOCS5 3′UTR as potential target of miR-432. [score:3]
A mutant was generated by deleting the targeting site of miR-432 present in 3′UTR of SOCS5 and cloned in the luciferase vector. [score:3]
To determine the effect of miR-432 on JAK-STAT pathway, miR-432 mimic was overexpressed along with scramble sequence as control and infected by JEV 24 hours post transfection. [score:3]
Further study is required to understand the expression of miR-432 in the in vivo conditions at later time points. [score:3]
miR-432 overexpression caused enhanced production of pro-inflammatory cytokines (IL-6 and TNF-α) (Supplementary Fig. 3A,C). [score:3]
This confirmed the targeting of 3′UTR of SOCS5 by miR-432. [score:3]
The overexpression and silencing of miR-432 was confirmed by real time PCR. [score:3]
Overexpression and silencing of Anti-miR-432. [score:3]
To validate the SOCS5 targeting by miR-432, the UTR clone of SOCS5 in luciferase vector along with miR-432 mimic was transfected in HeLa cells, which resulted into reduced luciferase activity. [score:3]
To generate the mutant clone, the binding site of miR-432 present in SOCS5 3′UTR (2242–2249) was deleted by using site directed mutagenesis. [score:2]
The overexpression and silencing of miR-432 was confirmed by real time PCR using miR-432 specific TaqMan primer and probe (# 4427975, Ambion). [score:2]
We found decrease in viral copies in miR-432 overexpressing cells as compared to scramble transfected cells (Fig. 4B). [score:2]
TaqMan probe specific to miR-432 were used to determine fold change. [score:1]
Human brain microglial cells were infected by JEV (MOI 5) and cells were harvested at various time points to determine miR-432 levels. [score:1]
In addition, we also checked the levels of miR-432 in JEV infected mice brain and we found decreased levels of miR-432 in brain of 2 day and 4 day infected mice. [score:1]
The seed region for mature miR-432 was found to be conserved in both human and mouse. [score:1]
cDNA was synthesized and miR-432 levels were determined by real time PCR. [score:1]
Scrambled seed sequence of miR-432 was transfected as control. [score:1]
To elucidate the effect of miR-432 on JEV replication, 100 pmol miR-432 mimic or scramble sequence was transfected into CHME3 cells and JEV infection was given 24 hours post transfection. [score:1]
Real time PCR (ABI VII A7 RT-PCR) was done by using miR-432 specific TaqMan probe (# 4427975, Ambion) and universal PCR master mix (#4324018; Applied Biosystems). [score:1]
To further confirm the specificity of this effect, anti-miR-432 was transfected into cells prior to JEV infection. [score:1]
The mutated UTR cloned in luciferase vector did not display any reduction of luciferase activity, when transfected along with miR-432 mimic. [score:1]
CHME3 cells were transfected with ISRE Luciferase reporter plasmid (1 μg) or along with miR-432 mimic, scrambled or anti-miR-432 (100 pmol). [score:1]
The seed sequence present in mature miR-432 of mouse and human are conserved, therefore we checked the levels of SOCS5 in JEV infected mice brain by western blotting and immunohistochemistry. [score:1]
Anti-miR-432 reduced STAT1 phosphorylation and lowered ISRE activity upon JEV infection, which led to the enhanced viral replication. [score:1]
CHME3 cells were transfected in 6 well plates with 100 pmol of miR-432 seed sequence mimic (Bioserve, Hyderabad, India) by using Lipofectamine 2000 (#11668-019; Invitrogen) according to manufacturer’s protocol. [score:1]
Graph shows decreased luciferase activity of the vector in presence of miR-432 mimic. [score:1]
miR-432 oligo and scramble sequence have been mentioned in Table 1. To silence miR-432, 100 pmol of anti-miR-432 (# AM17000, Ambion) was transfected and JEV infection was given 24 hours post transfection. [score:1]
To further visualize the effect of miR-432 downstream STAT1 phosphorylation, the ISRE activity was visualized by luciferase vector containing ISRE sequences at promoter site. [score:1]
The viral RNA was isolated from culture supernatant and viral copies were determined to check the effect of miR-432 on release of viral particles. [score:1]
CHME3 cells were transfected by 100 pmol of miR-432 mimic. [score:1]
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4
[+] score: 57
Inhibition of KRT83 expression by miR-432 was confirmed by both gene knockdown with siRNA and overexpression, which was consistent with the miRNAs and targets prediction results. [score:10]
Fig. 8The overexpression of miR-432 repressed the protein expression but not mRNA expression of KRT83 in primary sheep epidemial fiber cells. [score:7]
org/vert_71/) detected a conserved miR-432 -binding site in the CDS region of KRT83 mRNA, we thus used dual luciferase reporter system to test whether miR-432 could target KRT83 expression (Fig.   7). [score:5]
** indicates p < 0.01 To further examine the effect of miR-432 on expression of KRT83 at both RNA and protein level, we transfected primary sheep epidermal fiber cells with miR-432 mimic, and then compared the expression of KRT83 in cells with that in cells treated by negative control miRNA. [score:4]
** indicates p < 0.01To further examine the effect of miR-432 on expression of KRT83 at both RNA and protein level, we transfected primary sheep epidermal fiber cells with miR-432 mimic, and then compared the expression of KRT83 in cells with that in cells treated by negative control miRNA. [score:4]
KRT83 was direct targets of miR-432. [score:4]
At the RNA level, expression of both oar-miR-432 and KRT83 was lower in adult than lamb. [score:3]
a mRNA expression of KRT83 show no significant different between cells treated by miR-432 mimic and those treated by negative control miRNA. [score:3]
Fig. 7Hela cell culture transfections showing negative relationship between oar-miR-432 and target KRT83. [score:3]
The targets sequence of the predicted miR-432 binding site that includes CDS region of KRT83 gene were cloned from sheep genomic DNA and inserted into the psi-CHECK2 plasmid (Promega) using AsiI and pmeI restriction sites downstream from the Renilla luciferase gene. [score:3]
As shown in Fig.   8, after the same normalization with ACTB as housekeeping genes, qPCR showed no significant difference in KRT83 mRNA expression between miR-432 mimic and negative control treated cells, but western blotting showed significant decrease of KRT83 protein in cells treated by miR-432 mimic compared to those treated by negative control. [score:2]
Tan sheep miRNA-mRNA analysis Curly fleece Regulatory network KRT83 miR-432 Chinese Tan sheep (Ovis aries) are indigenous to Mongolian plateau and are usually found in the Ningxia Hui Autonomous Region and Gansu province in China. [score:2]
b Wester blotting showed decreased protein expression of KRT83 in cells treated by miR-432 mimic compared to those treated by negative control miRNA. [score:2]
However, there are also some miRNA -RNA pairs with positive correlation, such as oar-miR-432 and KRT83. [score:1]
To validate binding of miR-432 with KRT83, another primer was subsequently synthesized by Sangon (Shanghai, China) to introduce mutation of some bases at the 22 bp putative binding site of miR-432 in KRT83. [score:1]
For primary sheep epidermal fiber cells, miR-432 mimic (100 nM) was transfected into cells using Lipofectamine™ 2000 (Invitrogen), according to the manufacturer’s protocol, and cells were harvested 48 h post-transfection using for RNA and protein extraction. [score:1]
Cells were transfected with two plasmids containing wild type (wt) or mutant (mut) KRT-83 CDS region, and then treated with miR-432 mimic (black) or negative control (grey). [score:1]
Plasmids containing KRT83 CDS region were co -transfected with either miR-432 or negative control miRNA to each well at a concentration of 100 nM in triplicates (Lipofectamine, Invitrogen). [score:1]
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5
[+] score: 42
Set 2 is the list of predicted targets of miRs tested to not inhibit NALM6 growth (i. e. miR-550a, miR-873, miR-381 and miR-432) from TargetScan6.2 or miRDB, while Set 3 is the list of mRNA that is expressed in NALM6, as determined by genome-wide microarray profiling downloaded from the Cancer Cell Line Encyclopedia and its expression levels are denoted in the microarray dataset as “marginal” or “present”. [score:11]
First, we downloaded the sets of predicted mRNA targets of miR-509-5p and miR-509-3p (Set 1), as well as those of the 4 miRs that we had shown not to inhibit NALM6 growth (i. e. miR-381, miR-432, miR-550a and miR-873; Set 2) from the TargetScan6.2 [37] and/or miRDB [38], [39] miR target prediction databases. [score:9]
Since NALM6 cells transduced with miR-432∼136 did not result in miR-136 overexpression, we did not include miR-136 targets in Set 2 (Figure 4A). [score:5]
Similarly, overexpression of miR-381, miR-550a, miR-873, and miR-432 was achieved by lentiviral transduction (Figure S1E). [score:3]
We expressed the miR-432∼136 cluster as a single unit rather than as 2 individual miRs, to recapitulate the way they were screened and because the 2 miRs may cooperate. [score:3]
4 miRs (miR-381, miR-509, miR-550a, and miR-873) and 1 miR cluster (miR-432∼136) inhibited NALM6 growth in at least 2 of 3 replicate screens performed. [score:3]
However, no expression of miR-136 was detected in miR-432∼136 cluster-transduced NALM6 cells. [score:3]
These results indicate that miR-381, miR-432, miR-550a, and miR-873 do not inhibit growth of NALM6. [score:3]
NALM6 cells were individually transduced with lentivirus of (A) miR-381; (B) miR-550a; (C) miR-873 and (D) miR-432∼136 and empty vector (EV#1) to MOI  = 2. At 7 days after transduction, cells were mixed with mock-transduced cells to 50% GFP [+] cells and this was set as Day 0. The %GFP [+] cells (pre-gated on viable cells) of each culture were assessed weekly by flow cytometry for 35 days. [score:1]
Similarly, no change in %GFP [+] cells was observed over 35 days in thes for miR-381, miR-550a, miR-873 and miR-432∼136 (Figure S1A-S1D). [score:1]
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6
[+] score: 24
In lung adenocarcinoma, overexpression of miR-432 inhibited cell proliferation through arresting cell cycle by regulation of two directly targets E2F3 and AXL [60]. [score:9]
Similarly, in lung adenocarcinoma, miR-432 functioned as a tumor suppressor gene through targeting E2F3 and AXL [60]. [score:5]
It was also reported that downregulation of miR-432 was correlated with a higher clinical stage and poorer prognosis in lung adenocarcinoma patients [60]. [score:4]
Furthermore, depressed miR-432 could promote the disease progression, especially the drug resistance, though E2F3 and AXL. [score:3]
The findings highlighted the meaning of miR-432 dysfunction in promoting chemoresistance and implicated miR-432 as a promising molecular target for treating lung cancer [60]. [score:3]
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7
[+] score: 23
The results revealed that there were 128 miRNA-target genes shared between hsa-miR-34a and hsa-miR-449a, 1 target gene shared between hsa-miR-34a and hsa-miR-432, and 1 target gene shared between hsa-miR-432 and hsa-miR-449a (see Table S5 for the complete list). [score:7]
For the analyses of the predicted miRNA-target genes, 621 genes for three miRNAs (hsa-miR-34a, hsa-miR-449a, and has-miR-432) were obtained using MAMI [39] and 684 genes for two miRNAs (hsa-miR-34a and hsa-miR-449a) were obtained using TargetCombo [40] (see Table S4 for the setting in each method and the results for each miRNA). [score:5]
Three other miRNAs have also been implicated in neuropsychiatric disorders or neurodevelopment, e. g., miR-432 with autism in human cerebella cortex [48], miR-449 with Alzheimer's disease in cerebrospinal fluid [49], and miR-652 with embryogenesis in the mouse brain and spinal cord [31]. [score:4]
To confirm the comparability of TLDA -based genome-wide profiling with individual quantifications, we randomly chose 10 patients and 10 controls from the learning set and further quantified these subjects' expression levels of five miRNAs (has-miR 34a, miR-432, miR-548d, miR-659 and miR-185) using quantitative RT-PCR. [score:3]
Figure S3The relations in the five miRNAs (has-miR 34a, miR-432, miR-548d, miR-659 and miR-185) expression levels between two platforms of miRNA quantification, the array -based TLDA vs. [score:3]
From these a seven-miRNA signature (miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652) was identified using stepwise logistic regression analysis, with a fold-change ranging from −1.4 to 2.5 (Table 1 ). [score:1]
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8
[+] score: 20
A study examining the plasma levels of nine candidate miRNAs in plasma both at baseline and after 6 weeks of treatment showed expression of hsa-miR-181b, but not hsa-miR-34a and hsa-miR-432, was downregulated following treatment. [score:6]
[17] Although the relative expression of only two miRNAs (hsa-miR-34a and hsa-miR-449a) reached statistical significance in the peripheral sample, the remaining four, except hsa-miR-432, tended to be upregulated. [score:6]
In addition, downregulation of hsa-miR-432 in PBMC [18] and cortical hsa-miR-652 [22] have since been reported in people with schizophrenia. [score:4]
Intriguingly, the finding of another peripheral study using a cohort of preterm infants and adults [35] showed that six (hsa-miR-34a, hsa-miR-449a, hsa-miR-564, hsa-miR-432, hsa-miR-548d and hsa-miR-572) of the seven schizophrenia -associated miRNAs were consistently expressed from infancy to adulthood. [score:3]
We previously identified a seven-miRNA (hsa-miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652) signature as a potential biomarker for schizophrenia. [score:1]
[1 to 20 of 5 sentences]
9
[+] score: 16
We found that miR-432, miR-1286, miR-641, miR-1290, miR-1287 and miR-95 were highly upregulated just in cells with HPV infection upon 5-AZA treatment, whereas miR-625 was significantly downregulated (P<0.05) (Figure  3). [score:7]
However, in human pituitary GH adenomas, miR-432 plays a role as tumor suppressor gene by regulating HMGA2 (D’Angelo D, et al., [13]). [score:4]
Several analysis revealed high expression level of miR-432 which remained significant as independent predictor for recurrence-free (RFS) of hepatocellular carcinoma (Huang YH, et al., [12]). [score:3]
We found hypermethylation of miR-432, miR-1286, miR-641, miR-1290, miR-1287 and miR-95 may have some relationship with HPV infection in cervical cell lines. [score:1]
MiR-432, miR-1286, miR-641, miR-1290, miR-1287 and miR-95 were found up-modulated in Caski, Hela and Siha but not in C33A induced on treatment, while miR-625 was down-modulated. [score:1]
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10
[+] score: 13
Further studies showed that overexpression of miR-34b and miR-548c-3p can reduce the expression level of HMGA1 and HMGA2 proteins, and overexpression of miR-23b, miR-326, miR-432, and miR-570 could decrease the expression of HMGA2 as well [23]. [score:9]
MiR-23b [26], miR-326, miR-432, and miR-570 are predicted to target HMGA2, whereas miR-34b and miR-548c-3p can bind to HMGA1 and HMGA2 directly. [score:4]
[1 to 20 of 2 sentences]
11
[+] score: 13
Eighteen miRNAs, including miR-34b, miR-326, miR-432, miR-548c-3p, miR-570, and miR-603, were drastically and constantly downregulated in GH adenomas, whereas only miR-320 was significantly upregulated. [score:7]
miR-34b and miR-548c-3p were demonstrated to regulate both HMGA1 and HMGA2 expression, whereas miR-326, miR-432, and miR-570 target HMGA2 only. [score:6]
[1 to 20 of 2 sentences]
12
[+] score: 10
Accordingly, the analysis of a miRNA expression profile of GH adenomas versus normal pituitary has unveiled a set of miRNAs constantly deregulated in somatotroph tumors, comprising miR-326, miR-432, and miR-570, targeting HMGA2, miR-34b, and miR-548c-3p both having HMGA1 and HMGA2 as targets, and miR-326 and miR-603 targeting E2F1. [score:10]
[1 to 20 of 1 sentences]
13
[+] score: 10
Regarding translocation t(4;14), three miRNAs are differentially expressed, i. e. miR-135a, miR-596, and miR-432*, being significantly down-regulated when a t(4;14) is present with a maximal FC of 1.9 (Supplementary Table S6B). [score:6]
Comparison of myeloma cells to cells from MGUS-patients revealed three differentially expressed miRNAs (0.5%), i. e. miR-200b*, miR-432 and miR-486-3p (Supplementary Table S3). [score:3]
Four miRNAs are significantly positively associated and correlate with the University of Medical Sciences (UAMS) 70-gene risk-score, i. e. miR-135b, miR-432*, miR-583, and miR-596 (Supplementary Table S4, S5). [score:1]
[1 to 20 of 3 sentences]
14
[+] score: 9
Of these, 14 (miR-23b, miR-28, miR-98, miR-103, miR-107, miR-193a,0, miR-324-5p, miR-324-3p, miR-331, miR-374, miR-432, miR-502, and miR-660) were upregulated and 6 (miR-31, miR-451, miR-452, miR-565, miR-594 and miR-659) were downregulated. [score:7]
[27]↓quail myoblasts diff, ↓ C2C12 diff [29] ↓ C2C12 diff [28] ↓ muscle development [32]40miR-320↓(this study)↑ pMyo diff [33]  41 miR-324-3p (n)↑↑(this study)   42 miR-324-5p (n)↑(this study)   43 miR-331 (n)↑(this study)-  44miR-339↓(this study)↑ C2C12 diff [33] ↑ pMyo diff [33]  45miR-361↑(this study)↑ pMyo diff [33]  46 miR-362↑↑(this study)↑ C2C12 diff [28]  47 miR-374 (n)↑(this study)   48 miR-432 (n)↑(this study)   49 miR-451 (n)↓↓↓(this study)   50 miR-452 (n)↓↓(this study)   51 miR-500↑↑(this study)↑ C2C12 diff [28, 33] ↑ pMyo diff [33]  52 miR-501↑↑↑(this study)↑ C2C12 diff [28, 33]  53 miR-502 (n)↑↑(this study)-  54 miR-503↑(this study)↑ C2C12 diff [19, 28, 33] ↑ pMyo diff [33]  55 miR-532↑↑(this study)↑ C2C12 diff [28, 33] ↑ pMyo diff [33]  56↓↓ pMyo diff. [score:2]
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15
[+] score: 8
Control animals, however, also displayed similar miR-205 increases (2-fold) and miR-432 decreases (2-fold) at the 6 month time-point but were also accompanied by subtle increases (~1.5 fold) in expression for miR-27a, miR-92b, miR-10b, miR-143 and miR-126-5p (Table 3). [score:3]
All these miRNAs were significantly differentially expressed within the control group but, only miR-205 and miR-432 were identified as significant in the MAP-infected group. [score:3]
Specifically at the latter interval, miR-205 was increased (2-fold) while miR-432 was decreased (2-fold). [score:1]
Comparing the 0 to the six month time-points within each group revealed similar read count profiles for miR-205, miR-10b, miR-92b, miR-432, miR-27a, miR-127, miR-126 and miR-143. [score:1]
[1 to 20 of 4 sentences]
16
[+] score: 8
Differential expression analysis between the validation group and RRMS samples identified eight out of nine significantly dysregulated miRNAs as identified previously (miR-15b-5p, miR-23a-3p, miR-223-3p, miR-374a-5p, miR-30b-5p, miR-433-3p, miR-485-3p, miR-342-3p, miR-432-5p) (Table  3). [score:4]
Differential expression analysis between this new group and healthy controls confirmed that three of the four original miRNAs (miR-370-3p, miR-409-3p, miR-432-5p) were significantly dysregulated. [score:4]
[1 to 20 of 2 sentences]
17
[+] score: 6
Ma M. Wang X. Chen X. Cai R. Chen F. Dong W. Yang G. Pang W. MicroRNA-432 targeting E2F3 and P55PIK inhibits myogenesis through PI3K/AKT/mTOR signaling pathwayRNA Biol. [score:4]
Another study in myoblasts demonstrated that miR-432 is a negative regulator of myoblast proliferation and differentiation through the modulation of the PI3K/AKT/mTOR pathway [127]. [score:2]
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[+] score: 5
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-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-26a-1, hsa-mir-29a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-99a, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-197, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-10a, hsa-mir-34a, hsa-mir-182, hsa-mir-199a-2, hsa-mir-205, hsa-mir-210, hsa-mir-221, hsa-mir-223, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-140, hsa-mir-142, hsa-mir-143, hsa-mir-125b-2, hsa-mir-134, hsa-mir-146a, hsa-mir-150, hsa-mir-206, hsa-mir-155, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-101-2, hsa-mir-130b, hsa-mir-26a-2, hsa-mir-361, hsa-mir-362, hsa-mir-363, hsa-mir-376c, hsa-mir-371a, hsa-mir-375, hsa-mir-376a-1, hsa-mir-378a, hsa-mir-342, hsa-mir-151a, hsa-mir-324, hsa-mir-335, hsa-mir-345, hsa-mir-423, hsa-mir-483, hsa-mir-486-1, hsa-mir-146b, hsa-mir-202, hsa-mir-494, hsa-mir-495, hsa-mir-193b, hsa-mir-497, hsa-mir-455, hsa-mir-545, hsa-mir-376a-2, hsa-mir-487b, hsa-mir-551a, hsa-mir-571, hsa-mir-574, hsa-mir-576, hsa-mir-606, hsa-mir-628, hsa-mir-629, hsa-mir-411, hsa-mir-671, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-889, hsa-mir-876, hsa-mir-744, hsa-mir-885, hsa-mir-920, hsa-mir-937, hsa-mir-297, hsa-mir-1233-1, hsa-mir-1260a, hsa-mir-664a, hsa-mir-320c-2, hsa-mir-2861, hsa-mir-378b, hsa-mir-1260b, hsa-mir-378c, hsa-mir-1233-2, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-664b, hsa-mir-378j, hsa-mir-486-2
Expression profiling of circulating miRNAs via miRNA-seq showed differential expression of miR-205 and miR-432, but a signature of infection could not be identified (223). [score:5]
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[+] score: 5
The expression levels of 12 miRNAs, including miR-139-3p, miR-204, miR-760, miR-432, miR-524-5p, miR-136, miR-548d-3p, miR-206, miR-214, miR-383, miR-224, and miR-887 were significantly lower, whereas the expression level of miR-146a was significantly higher, in Jurkat cells after being cultured with TNF-α for 7 days (fold change > 4, p < 0.05, Fig.   1b). [score:5]
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[+] score: 4
The rest of co-expressed clusters were listed for regions at 6q13 (including mir-30a and mir-30c-2), Xp11.23 (including mir-362, mir-500, mir-501, mir-502 and mir-532), 14q32.2 (including mir-134, mir-379 and mir-382), 14q32.31 (including mir-127, mir-432 and mir-770), 9q22.32 (including let-7d, mir-23b and mir-27b) and 7q22.1 (including mir-93 and mir-106b) (Table 3). [score:3]
Loss of regions including 14q32.2 (location of mir-127, mir-432 and mir-770) and 14q32.31 (mir-134, mir-379, and mir-382) were reported in previous studies of renal cancer and osteosarcoma [16], [44]. [score:1]
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[+] score: 4
For miR-432, miR-411, miR 376-a, miR-381 and miR-487b, higher expression was associated with a lower relapse free probability. [score:3]
Five of these (miR- 376a, miR-381, miR-411, miR-432 and miR-487) map to human chromosome 14q32.31. [score:1]
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[+] score: 3
A signature of 5 miRNAs (miR-376a, miR-381, miR-411, miR-432, and miR-487) along with miR-203 that can be mapped to both chromosome 14q32.1 and 14q32.33 is shown in ependymoma and other tumours to be regulated by DNA methylation, proving the global dysregulation of this chromosome in carcinomas [143, 149, 150]. [score:3]
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[+] score: 3
In the Dlk1-Dio3 region, the maternally expressed genes can produce non-coding RNAs, including mir-431, mir-433, mir-127, mir-432 and mir-136. [score:3]
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[+] score: 3
Within the high homology regions, we found perfectly conserved seed matches for miRNAs that have been predicted (miR-103, miR-142-3p, miR-370, and miR-432) or already demonstrated (miR-15 [31], miR-16 [31], miR-26a [32], miR-214 [33], miR-548c-3p [34] and miR-761 [33]) to target the HMGA1 gene (Figure 1B and 1C). [score:3]
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[+] score: 3
662.00E-03 hsa-miR-432−1.803.00E-03 hsa-miR-1821.662.00E-03 hsa-miR-328−1.643.00E-03 hsa-miR-1441.423.00E-03    hsa-miR-146b1.424.00E-03    hsa-miR-182*1.614.00E-03    hsa-miR-1491.534.00E-03    hsa-miR-1411.674.00E-03    hsa-miR-610 1.34 5.00E-03       Negative Fold-Change indicates over -expression in margins. [score:3]
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[+] score: 2
In this work, the SVM method selected hsa-miR-146a-5p, hsa-miR-18b-5p, hsa-miR-21-3p, hsa-miR-22-3p, hsa-miR-29a-3p, hsa-miR-432-5p, hsa-miR-511-5p, and hsa-miR-596 as an EVD classifier. [score:1]
Six of the miRNAs increased in abundance with higher viral load (>1000 PFU), while miR-18b-5p and miR-432-5p declined (Fig. 4A). [score:1]
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[+] score: 2
However the results include many miRNAs not previously identified as senescence -associated: for example, mir-432 is highly induced by senescence (Fig. 2A), mir-145 is repressed (Fig. 2B), and others are depicted in Fig. 3. 10.1371/journal. [score:1]
However the results include many miRNAs not previously identified as senescence -associated: for example, mir-432 is highly induced by senescence (Fig. 2A), mir-145 is repressed (Fig. 2B), and others are depicted in Fig. 3. 10.1371/journal. [score:1]
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[+] score: 2
To further evaluate miRNA mimics on the inhibition of cell proliferation in A2780, we selected top 10 anti-proliferative miRNAs (miR-7, miR-124a, miR-192, miR-193a, miR-193b, miR-199a [*], miR-432 [*], miR-497, miR-506 and miR-517c) from the first screen, and examined the cell viability in A2780 cells transfected with different concentrations of miRNAs (5, 25, 50 nM). [score:1]
We discovered pro-proliferative miRNAs (miR-9 [*], miR-93, miR-130a, miR-130b, miR-301, miR-302b, miR-302d, miR-363, miR-372, miR-373), and anti-proliferative miRNAs (miR-7, miR-124a, miR-192, miR-193a, miR-193b, miR-199a [*], miR-432 [*], miR-497, miR-506, miR-517c) in A2780 cells. [score:1]
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[+] score: 2
Other miRNAs from this paper: hsa-mir-188, hsa-mir-296, hsa-mir-328, hsa-mir-331
Mir-432, Mir-188, and Mir-331 target each have putative binding sites in the 3' UTR of >8 EC-restricted genes. [score:2]
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[+] score: 2
Sequences 200 nucleotides upstream to the transcription start site of miR-654, miR-431, miR-127, miR-432, miR-411, miR-544, miR-369-3p, miR-382 and miR-134 were then amplified using qPCR from DNA present in the immune complexes. [score:1]
Similarly, methylation patterns of the individual OS samples showed either no significant change or partial hypomethylation patterns at miR-431, miR-432 upstream regions, relative to normal bone tissues (Figure 1). [score:1]
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[+] score: 1
From the prediction, the experimental data from cow milk study validated 9 transportable milk miRNAs in human blood, including bta-miR-487b, miR-181b, miR-421, miR-215, let-7c, miR-301a, miR-432, miR-127, and miR-184. [score:1]
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[+] score: 1
The normalized RT-PCR data of three additional miRNAs (miR-432, miR-210 and miR-186) are seen to the right, sharing the same color scheme as the histograms. [score:1]
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[+] score: 1
3/3p21.32 −3.91 hsa-miR-487b 14q32.2 −3.82(29) hsa-miR-487a 14q32.2 −3.78 hsa-miR-758 14q32.2 −3.65 hsa-miR-485-5p 14q32.2 −3.60 hsa-miR-138-1* 16q13.3/3p21.32 −3.55 hsa-miR-382 14q32.2 −3.53(12, 29) hsa-miR-504 Xq26.3 −3.45(52) hsa-miR-128 2q21.3/3p22.3 −3.43(12, 14, 51, 59) hsa-miR-490-5p 7q33 −3.42 hsa-miR-770-5p 14q32.2 −3.35 hsa-miR-410 14q32.2 −3.30(29) hsa-miR-432 14q32.2 −3.29 hsa-miR-485-3p 14q32.2 −3.02 hsa-miR-490-3p 7q33 −2.88 hsa-miR-381 14q32.2 −2. [score:1]
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[+] score: 1
In addition, several miRNAs were significantly decreased (miR432 (0.09-fold), miR-700 (0.1-fold), miR-692-1 (0.35-fold)) which could also contribute to relieved post-transcriptional gene repression. [score:1]
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[+] score: 1
Additionally, miR-202 miR-423-5p miR-503 miR-184 and miR-922 bind also to the conserved binding region chromosome 15 positions 58889443–5889473 and miR-330-5p (chr15:58889149–58889178), miR-671-5p (chr15:58889720–58889745) and miR-432 (chr15:58889688–58889718) bind to a region with good conservation also to the far related species zebra fish, but these eight miRNAs have no indication to be involved in AD (Table  1). [score:1]
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[+] score: 1
1 −2.0 −4.2 miR-410 −2.4 −1.7 −4.2 miR-424 −4.1 −2.6 −10.7 miR-424* −1.2 −4.0 −4.9 miR-431 2.2 −4.3 −1.9 miR-432 −1.9 −2.4 −4.6 miR-503 −8.6 −3.2 −27.3 miR-542-3p −3.2 −2.1 −6.9 miR-542-5p −2.0 −3.1 −6.1 miR-596 2.2 −4.4 −2.0 miR-610 1.9 −5.1 −2. [score:1]
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[+] score: 1
The proliferation effects of miR-9, miR-196b, and miR-432 were not consistent in all cell lines and were therefore left out from further validation. [score:1]
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[+] score: 1
The exceptions (cfa-miR-432, -499, and -212) could not be differentiated between tissues analyzed by Q-RT-PCR. [score:1]
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[+] score: 1
miR-127 is located in chromosome region 14q32.2 and belongs to a cluster that includes miR-431, miR-433, miR-127, miR-432, and miR-136 [10]. [score:1]
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[+] score: 1
In total, eight circulating miRNAs (hsa-miR-146a-5p, hsa-miR-18b-5p, hsa-miR-21-3p, hsa-miR-22-3p, hsa-miR-29a-3p, hsa-miR-432-5p, hsa-miR-511-5p, and hsa-miR-596) were selected as an EBOV classifier. [score:1]
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[+] score: 1
Several recent reports have highlighted the post-transcriptional repression of HMGA proteins by non-coding RNAs and, in particular, numerous miRNAs with this activity have been identified (let-7a, miR-15, miR-16, miR-26a, miR-34b, miR-196a2, miR-326, miR-432, miR-548c-3p, miR-570, miR-603) (53, 54). [score:1]
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[+] score: 1
Mononuclear leukocyte -based miR profiling identified seven miRs, that is, miR-34a, miR- 449a, miR-564, miR-432, miR-548d, miR-572, miR-652 and had a high discriminating accuracy for schizophrenia. [score:1]
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