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56 publications mentioning rno-mir-27a

Open access articles that are associated with the species Rattus norvegicus and mention the gene name mir-27a. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 380
Other miRNAs from this paper: rno-mir-29c-1, rno-mir-192, rno-mir-377, rno-mir-29c-2
Downregulation of miR-27a with a miR-27a inhibitor prevented high glucose (HG) -induced mesangial cell (MC) proliferation and the expression of ECM -associated profibrotic genes via upregulation of PPARγ expression. [score:13]
Moreover, when the miR-27a expression vector was cotransfected with the miR-27a -inhibitor vector and the wild type PPARγ-3′-UTR, the miR-27a inhibitor significantly counteracted miR-27a -mediated luciferase downregulation. [score:10]
Recently, it was reported that miR-27a could directly bind to the 3′-UTR of PPARγ mRNA and suppress PPARγ expression, thereby suppressing adipocyte differentiation 14. [score:8]
As expected, miR-27a inhibitor suppressed the HG -dependent upregulation the levels of these ECM -associated profibrotic genes. [score:8]
Importantly, knockdown of PPARγ abrogated the effects of miR-27a inhibitor on MC proliferation and profibrotic gene expression, indicating the critical role of PPARγ as a target of miR-27a in both HG -induced cell proliferation and ECM accumulation in rat kidney MCs. [score:8]
Inhibition of miR-27a suppressed HG -induced downregulation of PPARγ in HG -treated MCs. [score:8]
Upregulation of miR-27a expression under hyperglycaemic conditions both in vitro and in vivo In vitro and diabetic animal mo del studies have confirmed the beneficial role of PPARγ in diabetic kidney disease 27 28. [score:8]
Expression of miR-27a is upregulated by high glucose, and targets the PPARγ gene. [score:8]
Together with our findings indicated that alterations in miR-27a levels could regulate PPARγ levels (Fig. 2), these data demonstrate that HG -induced cell proliferation and ECM accumulation may be prevented by the inhibition of miR-27a, and that this is likely due to the consequent up-regulation of PPARγ. [score:7]
Further, miR-27a upregulation led to enhanced cell proliferation and ECM accumulation through PPARγ downregulation. [score:7]
In addition, the PPARγ upregulation observed following miR-27a knockdown was associated with decreased MC proliferation and reduced expression of profibrotic genes. [score:7]
Inhibition of miR-27a with antagomir-27a reduces miR-27a expression, attenuates proteinuria, and increases PPARγ expression in STZ -induced diabetic rats. [score:7]
The miR-27a mimic, a miRNA negative control (NC mimic), miR-27a inhibitor, and miRNA inhibitor negative control (NC inhibitor) were designed and synthesized by GenePharma (Shanghai, PRC). [score:7]
Our results also indicated that miR-27a was capable of targeting the PPARγ 3′-UTR to inhibit PPARγ expression. [score:7]
Upregulation of miR-27a expression under hyperglycaemic conditions both in vitro and in vivo. [score:6]
The result is in agreement with previous data showing that miR-27a downregulation suppresses cell growth in vitro 30. [score:6]
Importantly, HG -induced downregulation of PPARγ was reversed when MCs were transfected with a miR-27a inhibitor (Fig. 2B–E). [score:6]
Here, we found that miR-27a expression was consistently upregulated in rat MCs exposed to HG and in kidney glomeruli from STZ -induced diabetic rats. [score:6]
Consistent with these in vitro results, there was a decrease in miR-27a expression and a corresponding increase in PPARγ expression in antagomir-27a -treated diabetic rats; this reduced cell proliferation, and inhibited ECM accumulation compared with untreated diabetic rats and negative control rats. [score:6]
As shown in Fig. 1B, miR-27a expression was significantly upregulated in rat kidney MCs exposed to HG (25 mM glucose). [score:6]
To determine the in vivo relevance of miR-27a knockdown on PPARγ expression in the kidneys of STZ -induced rats, we examined the expression of PPARγ mRNA and protein levels in the kidney glomeruli of antagomir-27a -treated rats. [score:6]
Furthermore, miR-27a is highly expressed in the kidneys 14, and is also upregulated in patients with type 1 or 2 diabetes 11 12. [score:6]
These results clearly indicate that miR-27a directly specifically binds to the 3′-UTR of PPARγ and suppress PPARγ expression. [score:6]
These results demonstrate that the inhibition of endogenous miR-27a by antagomir-27a and subsequent increase in PPARγ levels triggers the downregulation of several genes that play key profibrotic roles in diabetic rats. [score:6]
Therefore, miR-27a is likely to be relevant in DN pathology, and is potentially an important therapeutic target for treating diabetic renal diseases. [score:5]
Furthermore, our data suggest that antagomir -based miRNA inhibitors (such as antagomir-miR-27a) can efficiently and specifically reduce renal miR-27a levels, renal hypertrophy, profibrotic gene expression, and renal fibrosis in diabetic rats. [score:5]
Inhibition of miR-27a with antagomir-27a reduces the expression of profibrotic genes and ECM proteins in the kidney glomeruli of STZ -induced diabetic rats. [score:5]
Although the regulatory influences of miR-27a remain incompletely defined, our data reveal that its overexpression clearly affects DN development. [score:5]
In contrast, suppression of miR-27a activity with the miR-27a inhibitor increased PPARγ immunofluorescence in HG -treated MCs (Fig. 2F,G). [score:5]
Importantly, inhibition of miR-27a with a miR-27a inhibitor in vitro or with antagomir-27a in vivo prevented HG -induced MC proliferation and ECM accumulation. [score:5]
In contrast, the effect of miR-27a inhibitor was significantly decreased when HG -treated MCs were transfected with the miR-27a inhibitor and PPARγ siRNA (Fig. 3D–J). [score:5]
Interestingly, the expression of miR-27a increased while PPARγ expression decreased in HG -treated MCs. [score:5]
While miR-27a is reportedly upregulated in the serum of patients with type 1 or 2 diabetes 11 12, there have been no reports of pathological roles of miR-27a in DN to date. [score:4]
In addition, the proliferation of miR-27a inhibitor -transfected MCs was significantly inhibited compared with HG -treated MCs and negative control cells. [score:4]
miR-27a negatively regulates PPARγ expression. [score:4]
Importantly, we showed that the knockdown of miR-27a with antagomir-27a significantly increased PPARγ expression. [score:4]
miRNA-27a expression was quantified using miRNA-specific PCR primers and probe and the TaqMan Gene Expression Master Mix (Applied Biosystems, USA) on an Applied Biosystems 7500 Fast Sequence Detection System (Applied Biosystems). [score:4]
Together, these findings indicate that increased miR-27a expression may be involved in the initial cellular responses to hyperglycaemia, which could eventually result in the development of diabetes. [score:4]
miR-27a is upregulated in cultured adipocytes exposed to hyperglycaemia 13. [score:4]
To test whether they would be effective in DN, we used a chemically modified antisense oligonucleotide (antagomir-27a) to knock down miR-27a expression in vivo. [score:4]
Taken together, these results highlight miR-27a as an important regulator of PPARγ expression in DN. [score:4]
To examine the potential relevance of miR-27a upregulation in DN, we utilized a STZ -induced diabetes mo del in rats. [score:4]
Knockdown of miR-27a protects renal function in STZ -induced diabetic rats and ameliorates DN progression in vivoBased on our in vitro data, we hypothesized that miR-27a inhibition in vivo might protect renal function in STZ -induced diabetic rats. [score:4]
As shown in Fig. 4A, miR-27a expression in kidney glomeruli was significantly suppressed in antagomir-27a -treated diabetic rats, compared with untreated diabetic rats. [score:4]
Therefore, we hypothesized that increased miR-27a levels may provide the mechanistic explanation for reduced PPARγ expression. [score:3]
25 mM glucose + miR-27a inhibitor. [score:3]
We next examined whether a miR-27a inhibitor would have the opposite effect. [score:3]
To confirm the impact of miR-27a on PPARγ expression, MCs were transfected with a miR-27a mimic. [score:3]
Relative expression of miR-27a was analysed using the 2 [−ΔΔCT] method 23. [score:3]
MCs were seeded onto chamber slides and transfected with the miR-27a mimic, the miR-27a inhibitor, or a negative control miRNA. [score:3]
How to cite this article: Wu, L. et al. MicroRNA-27a Induces Mesangial Cell Injury by Targeting of PPARγ, and its In Vivo Knockdown Prevents Progression of Diabetic Nephropathy. [score:3]
Taken together, these findings suggest that increased miR-27a levels may explain previously reported reductions of PPARγ expression 20 29, which may in turn contribute to DN pathology. [score:3]
In this case, no significant changes in luciferase activity were observed upon overexpression of miR-27a or the negative control. [score:3]
Inhibition of miR-27a attenuates MC proliferation and ECM accumulation. [score:3]
Rat kidney mesangial cells were transfected with a miR-27a mimic under normal glucose (NG, 5.6 mM) conditions or a miR-27a inhibitor under high glucose (HG, 25 mM) conditions. [score:3]
miR-27a levels were normalized to U6 snRNA expression. [score:3]
Moreover, the in vivo inhibition of miR-27a protected diabetic renal function and ameliorated the progression of DN. [score:3]
Based on our in vitro data, we hypothesized that miR-27a inhibition in vivo might protect renal function in STZ -induced diabetic rats. [score:3]
In contrast, when HG -treated MCs were transfected with both the miR-27a inhibitor and PPARγ siRNA, the effect of miR-27a on cell growth was enhanced (Fig. 3A). [score:3]
These findings provide new insights into the role of miR-27a in diabetes and indicate that miR-27a inhibitors may be useful for the treatment of DN. [score:3]
In addition, we show that miR-27a is a novel regulator of MC proliferation and ECM accumulation through the post-transcriptional regulation of PPARγ. [score:3]
These data further support the renoprotective effects of miR-27a inhibition in diabetic rats. [score:3]
These data indicate that mimic and inhibitor of miR-27a had the opposite effect on ECM accumulation. [score:3]
To determine the specificity of this result, MCs were cotransfected with the mutant PPARγ-3′-UTR vector and the miR-27a overexpression vector in MCs. [score:3]
MCs were plated at a density of 5,000 cells/well in 96-well plates, and subsequently transfected with the miR-27a inhibitor, PPARγ siRNA, or negative controls at a final concentration of 50 nM. [score:3]
Furthermore, our results demonstrated that a miR-27a mimic significantly reduced PPARγ expression in NG -treated MCs. [score:3]
In addition, upregulation of miR-27a by miR-27a mimic increased the levels of these profibrotic genes, compared with NG group. [score:3]
PPARγ is a target of miR-27a. [score:3]
Our integrated in vitro and in vivo studies indicated that miR-27a expression was significantly increased in these tissues and cell types. [score:3]
Rat kidney MCs were transfected with PPARγ siRNA in the presence of NG levels (5.6 mM) conditions, or with a miR-27a inhibitor and/or PPARγ siRNA in the presence of HG (25 mM). [score:3]
As shown in Fig. 1C, miR-27a expression was significantly increased in the kidney glomeruli of diabetic rats. [score:3]
MCs were transfected using Lipofectamine2000 with final concentrations of 50 nM miR-27a mimic or miR-27a inhibitor and/or PPARγ siRNA. [score:3]
However, the effect of HG was reversed by miR-27a inhibition. [score:3]
To determine whether miR-27a is a key regulatory factor in DN, we examined its levels in samples obtained from kidney glomeruli of STZ -induced diabetic rats and in kidney MCs exposed to hyperglycaemic conditions. [score:2]
As shown in Fig. 1D, miR-27a suppressed activity of the wild type PPARγ-3′-UTR luciferase-reporter construct by 50% compared with cells cotransfected with a negative control. [score:2]
These results demonstrate that endogenous miR-27a levels are efficiently knocked down by antagomir-27a in vivo, and that this is associated with renoprotective effects in diabetic rats. [score:2]
These data indicate that miR-27a negatively regulates PPARγ, and in doing so, triggers enhanced MC proliferation and ECM accumulation. [score:2]
Knockdown of miR-27a protects renal function in STZ -induced diabetic rats and ameliorates DN progression in vivo. [score:2]
Similarly, miR-27a can bind to the PPARγ 3′-UTR in human pulmonary artery endothelial cells and regulate cell proliferation 17. [score:2]
For luciferase assays, rat kidney MCs were cotransfected with the pEZX-MT05 vector with a PPARγ-3′-UTR (GeneCopoeia RmiT049429-MT05) or a mut-PPARγ-3′-UTR (GeneCopoeia CS-RmiT049429-MT05), the pEXZ-MR03 vector encoding the miR-27a mimic (GeneCopoeia RmiR6129-MR03), and the pEXZ-AM03 vector encoding the miR-27a inhibitor (GeneCopoeia RmiR-AN0359-AM03), using the EndoFectin Lenti Transfection Reagent (Cat. [score:2]
Antagomir-27a or miR-27a mismatch mutations (NC antagomir) were administered to diabetic rats (n = 5, respectively) by intravenous injection at doses of 100 nM in 0.2 mL twice a week for 8 weeks. [score:2]
To verify that miR-27a binds directly to the 3′-UTR of PPARγ, we inserted the rat PPARγ-3′-UTR (with the normal miR-27a binding site sequence or a mut-PPARγ-3′-UTR) into the pEZX-MT05 vector, which was then transfected into rat kidney MCs. [score:2]
Rno, Rattus norvegicus; Mmu, Mus musculus; Hsa, Homo sapiens; Cfa, Canis lupus familiaris; Gga, Gallus gallus domesticus; rno -miR-27a, Rattus norvegicus- miR-27a. [score:1]
Moreover, miR-27a levels are strongly and positively correlated with fasting glucose levels in patients with type 2 diabetes 12. [score:1]
This analysis indicated that miR-27a has a high probability of binding the 3′-UTR of PPARγ mRNA and that the putative miR-27a binding sites in the PPARγ-3′-UTR are highly conserved between several mammals, such as humans, mice, rats, chickens, and dogs (Fig. 1A). [score:1]
Thus, we focused on miR-27a in our experimental mo dels, both in vitro and in vivo. [score:1]
Lower panel, schematic illustration of miR-27a pairing with the rat PPARγ 3′-UTR. [score:1]
Because MCs contribute to the excessive accumulation of ECM proteins during DN, we next examined the effects of miR-27a on proteins relevant to this process. [score:1]
Taken together, the data presented in this study reveal for the first time the critical role of miR-27a in the response of MCs exposed to HG concentrations. [score:1]
NC antagomir did not affect miR-27a levels in diabetic rats. [score:1]
To further examine the effect of miR-27a on PPARγ, we performed immunofluorescence microscopy. [score:1]
As shown in Fig. 2, this lead to a clear increase in miR-27a levels in MCs (Fig. 2A) and a concomitant reduction in both PPARγ mRNA (Fig. 2C) and protein (Fig. 2D,E) levels. [score:1]
Taken together, these data indicate that To determine the role of miR-27a in MC proliferation, we next examined cell viability. [score:1]
The miR-27a seed sequence is shown in the gray box. [score:1]
We indeed confirmed that miR-27a bound to the PPARγ 3′-UTR in rat kidney MCs. [score:1]
Quantitative real time (qRT)-PCR for miR-27a. [score:1]
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2
[+] score: 305
Interestingly, the inhibition of miR-27a increased the PPARγ -induced down-regulation of α-SMA and COL1A2 protein levels (Figure 7D), suggesting that miR-27a is involved in the activation induced by TGFβ1 in HSCs through the up-regulation of α-SMA and COL1A2 expression by targeting PPARγ. [score:13]
Furthermore, the expression of α-SMA and COL1A2, markers of fibrogenic cell activation, was up-regulated in TGFβ1 -treated LX2 cells (Figure 6B), but this effect was significantly reduced by the inhibition of miR-27a expression (Figure 6B). [score:10]
miR-27a targeted PPARγ and inhibited PPARγ -induced up-regulation of fibrosis-related gene expression. [score:10]
The overexpression of PPARγ prevents miR-27a from targeting FOXO1, APC, p53, and RXRα for their down-regulation. [score:8]
The overexpression of miR-27a inhibited the PPARγ -induced up-regulation of these fibrosis-related genes (Figure 7E). [score:8]
We found that the overexpression of miR-27a in HSCs also led to the significant down-regulation of PPARγ, FOXO1, APC, P53, and RXRα mRNAs expression in LX2 cells (Figure 7E). [score:8]
The miRNA profile analysis showed that 38 miRNAs were differentially expressed between the HBC and CHB subjects; 33 were up-regulated, including miR-27a, miR-27b, miR-142-3p, miR-151-5p and miR-424, and 5 were down-regulated in HBC patients compared with the levels in CHB patients (fold-change>2.0 and P<0.01) (Table 2). [score:8]
The overexpression of miR-27a inhibited the PPARγ -induced up-regulation of these fibrosis-related genes, including PPARγ, FOXO1, APC, P53, and RXRα (Figure 7E). [score:8]
The overexpression of miR-27a in HSCs led to significant up-regulation of α-SMA and COL1A2 expression levels (Figure 7C). [score:8]
Furthermore, the overexpression of miR-27a in LX2 cells also led to the significant down-regulation of PPARγ, FOXO1, APC, P53, and RXRα mRNAs expression (Figure 7E). [score:8]
Furthermore, similar to miR-27a inhibition, a PPARγ agonist significantly inhibited α-SMA and COL1A2 expression and attenuated the TGFβ -induced elevation of α-SMA and COL1A2 levels (Figure 7C). [score:7]
Inhibition of miR-27a attenuates HSCs proliferation and inhibits TGFβ -induced expression of fibrosis-related genes. [score:7]
In this study, we found that miR-27a expression was significantly up-regulated in human hepatic stellate LX2 cells and culture medium activated by TGFβ1 (Figure 5A and 5B), while miR-27a did not show specific regulation changes following TGFβ1 treatment in normal human hepatic L02 and hepatocellular carcinoma HepG2 cells and the culture medium (Figure 5A and 5B). [score:7]
We next explored the mechanisms responsible for the miR-27a -induced up-regulation of α-SMA and COL1A2 expression. [score:6]
miR-27a expression was up-regulated in response to TGFβ1 stimulation in LX2 cells and in the culture medium. [score:6]
To identify validated and predicted targets of miR-27a, we searched the miRTarBase and miRWalk databases, and found that miR-27a may regulate the expression levels of PPARγ, FOXO1, APC, P53, and RXRα. [score:6]
When human LX2 cells were stimulated with recombinant TGFβ1 (10 ng/ml), miR-27a expression was substantially up-regulated in LX2 cells and in the culture medium (Figure 5A and 5B). [score:6]
We found that miR-27a directly targeted PPARγ and promoted the expressions of profibrotic factors, such as α-SMA and COL1A2, in LX2 cells (Figure 7B and 7C). [score:6]
We found that miR-27a directly targets PPARγ and promotes the expression of profibrotic genes in LX2 cells. [score:6]
Interestingly, the inhibition of miR-27a increased the PPARγ -induced down-regulation of α-SMA and COL1A2 protein levels (Figure 7D). [score:6]
Serum miR-27a expression was up-regulated in rat mo dels of DMN -induced liver cirrhosis. [score:6]
The inhibition of miR-27a attenuated the TGFβ -induced expression of fibrosis-related genes (Figure 6B). [score:5]
miR-27a suppresses PPARγ expression and a PPARγ agonist attenuates the effect of TGFβ in LX2 cells. [score:5]
Our findings also suggest that miR-27a plays an important role in HSCs activation by targeting multiple target genes, including PPARγ, FOXO1, APC, P53, and RXRα. [score:5]
Moreover, miR-27a expression was well correlated with disease progression in the HBC subjects and was significantly higher in patients with decompensated HBC than in patients with compensated HBC (P=0.0009) (Figure 2C). [score:5]
Furthermore, we demonstrated the expression levels of serum miR-27a and miR-122 were markedly up-regulated in DMN -induced liver cirrhosis in rats compared to those in saline -treated rats (Figure 4A and 4B). [score:5]
Elucidating the miR-27a-targets regulatory network may shed light on liver fibrogenesis and may be valuable for the development of novel diagnostic and treatment approaches for liver fibrosis. [score:5]
MiR-27a is a direct regulator of PPARγ, FOXO1, APC, p53 and RXRα expression in HSCs. [score:4]
In summary, we found that miR-27a was significantly up-regulated in the serum of HBC patients, DMN -induced rat liver cirrhosis and TGFβ1-activated HSCs. [score:4]
Serum miR-27a was significantly up-regulated in HBC, which helped differentiate HBC from CHB and Ctrl samples (P<0.0001 for both) (Figure 2A). [score:4]
The serum miR-27a level was significantly up-regulated in HBC, and could differentiate HBC from CHB and Ctrl subjects (P<0.0001 for both) (Figure 2A). [score:4]
Validation in an independent cohort of individuals using quantitative RT-PCR (RT-qPCR) allowed us to confirm that the identified miR-27a was significantly up-regulated in the serum of patients with HBC or rats with DMN -induced liver cirrhosis, TGFβ1-activated hepatic stellate cells(HSCs) and the culture medium. [score:4]
Serum miR-27a level was up-regulated in HBC. [score:4]
Based on the prominent up-regulation of circulating miR-27a in HBC patients, we hypothesized that miR-27a might be centrally involved in cellular responses to profibrogenic signals. [score:4]
These results suggest that miR-27a up-regulation may facilitate the TGFβ -induced activation of HSCs. [score:4]
It was previously reported that miR-27a also regulates several target genes, such as FOXO1, APC, P53 and RXRα [17– 20], which are associated with liver fibrosis/cirrhosis [21– 24]. [score:4]
After 4 weeks of DMN treatment, the miR-27a and miR-122 concentrations in sera were significantly up-regulated compared to those of normal animals (P<0.0001) (Figure 4A and 4B). [score:3]
The relative miR-27a expression in L02, LX2, and HepG2 cells (A) and in the culture medium (B) was measured by RT-qPCR after treatment with 10 ng/ml TGFβ1 for 24 h. The results are expressed as the mean; error bars denote the standard error of the mean. [score:3]
As expected, we found that the introduction of miR-27a repressed PPARγ expression (Figure 7B) in LX2 cells. [score:3]
We found that miR-27a has a moderate effect on inhibiting the proliferation of HSCs (Figure 6A). [score:3]
More studies are needed to further define the mechanism of miR-27a -mediated growth inhibition of HSCs. [score:3]
Figure 7 (A) The expression level of miR-27a in LX2 cells infected with Lv-miR-27a. [score:3]
Figure 5The relative miR-27a expression in L02, LX2, and HepG2 cells (A) and in the culture medium (B) was measured by RT-qPCR after treatment with 10 ng/ml TGFβ1 for 24 h. The results are expressed as the mean; error bars denote the standard error of the mean. [score:3]
To identify the validated and predicted targets of miR-27a, we searched the miRTarBase (http://miRTarBase. [score:3]
MiR-27a has previously been demonstrated to regulate several target genes, such as FOXO1 [17], APC [18], P53 [19] and RXRα [20], which are associated with liver fibrosis/cirrhosis [21– 24]. [score:3]
We analyzed the expression levels of serum miR-27a and miR-122 in HBC, CHB, and Ctrl subjects by RT-qPCR for the subsequent experiments. [score:3]
We assessed the stimulatory effect of TGFβ1 on miR-27a expression in LX2 (a human HSC line), L02, and HepG2 cells and in the culture medium. [score:3]
We further identified, validated and predicted targets of miR-27a using the miRTarBase and miRWalk databases. [score:3]
Previous studies have reported that miR-27a promotes renal tubulointerstitial fibrosis [38], podocyte injury [39] and mesangial cell injury [40] by suppressing PPARγ in diabetic nephropathy. [score:3]
To determine whether serum miR-27a was over-expressed in HBC patients, miR-27a and miR-122 were identified as candidates for further testing via RT-qPCR of samples from 87 HBC, 64 CHB, and 36 Ctrl subjects. [score:3]
Emerging evidence suggests the importance of miR-27a overexpression in HSCs [20, 37], although the full molecular mechanisms have yet to be established. [score:3]
Our study demonstrated that circulating miR-27a could be a potential predictor for HSCs activation and the occurrence and development ofHBC. [score:2]
The proliferation of miR-27a antagomir -transfected LX2 cells was significantly inhibited compared to that of negative control cells (Figure 6A). [score:2]
These data support that miR-27a may be associated with the regulation of hepatic fibrogenesis. [score:2]
Although the role of miR-27a in rat HSCs activation has been reported [20], its effects on the occurrence and development of HBC remain unclear. [score:2]
LX2 cells were transfected with negative control (Con) or miR-27a antagomir (27I, 100 nM) for 48 hours, followed by stimulation with10 ng/ml TGFβ (+) or remained untreated (-) for 24 hours before immunoblotting. [score:1]
Comparing HBC subjects with CHB and Ctrl subjects, the ROC curve areas of miR-27a were 0.82 (95% CI: 0.75-0.88) (Figure 3A) and 0.87 (95% CI: 0.80-0.93) (Figure 3B), respectively. [score:1]
Figure 6 (A) LX2 cells were transfected with 100 nM miR-27a antagomir and a control antagomir. [score:1]
These results demonstrate that the level of miR-27a may distinguish HBC from CHB and Ctrl cases. [score:1]
We conclude that circulating miR-27a may be a more specific predictor for HBC than miR-122. [score:1]
For these experiments, 5 candidate miRNAs (miR-27a, miR-27b, miR-142-3p, miR-151-5p, and miR-424) were chosen because they were among in the 38 deregulated miRNAs in HBC compared with CHB. [score:1]
These findings provide evidence that PPARγ is a critical, intermediate, downstream modulator of miR-27a. [score:1]
Serum levels of miR-27a and miR-122 in CHB, HBC and Ctrl subjects. [score:1]
To determine the role of miR-27a in HSCs proliferation, we next examined LX2 cell viability. [score:1]
However, miR-27a did not exhibit specific changes following TGFβ1 stimulation in L02 and HEPG2 cells and in the culture medium. [score:1]
In brief, LX2 cells were cultured at a concentration of 3 [*]10 [3] cells/well in plastic plates for 24 hours and then transfected with the miR-27a antagomir, or negative controls at a final concentration of 100 nM. [score:1]
We speculated that the release of miR-27a from HSCs activated by TGFβ1 is the principal source of extracellular circulating miR-27a in HBC. [score:1]
The miR-27a antagomir, or a negative control of the antagomir (GenePharma, Shanghai, China) were transiently transfected into LX2 cells using Lipofectamine 3000 transfection reagent (Thermo Fisher Scientific) according to the manufacturer’s protocol. [score:1]
Lentiviral miR-27a (Lv-miR-27a) and empty lentiviral (Lv-Con) vectors were constructed by Genechem Company (Shanghai, China), and they were infected into LX2 cells according to the manufacturer’s instructions. [score:1]
To further assess whether differential miR-27a production was associated with rodent mo dels of liver cirrhosis, we used a rat mo del of DMN -induced liver cirrhosis. [score:1]
ROC curve analyses revealed that serum miR-27a may be a useful marker for discriminating between HBC and CHB. [score:1]
We focused on miR-27a to determine whether it can distinguish HBC from CHB and to identify the potential mechanisms. [score:1]
In this work, we focused mainly on the role of miR-27a in HSCs. [score:1]
Hepatic cell and culture medium miR-27a levels were normalized using RNU6 and cel-miR-39 as a reference, whereas serum miR-27a was normalized to miR-24 [13]. [score:1]
The sensitivity and specificity values of miR-27a were 82.8% and 80.6% in the HBC and Ctrl subjects, respectively, and the sensitivity and specificity were 66.7% and 84.4% in the HBC subjects and CHB subjects, respectively. [score:1]
The level of miR-27a significantly increased when LX2 cells were activated by TGFβ1 treatment (Figure 5A). [score:1]
On the other hand, miR-27a showed a good capacity to discriminate between the groups. [score:1]
The final concentration of the miR-27a antagomir or agomir and negative control of the antagomir or agomir was 100 nM. [score:1]
Serum levels of miR-27a and miR-122 in a rat mo del of liver cirrhosis induced by DMN and saline. [score:1]
The ROC curve area for the combination of miR-27a and miR-122 was 0.94 (Figure 3F). [score:1]
In particular, the ROC curve analyses suggested that using both miR-27a and miR-122 (ROC=0.94) was preferable to using miR-27a (ROC=0.82) or miR-122 (ROC=0.87) alone as a marker for discriminating between HBC and CHB. [score:1]
Circulating miR-27a could be a potential predictor for HBC and HSCs activation. [score:1]
Figure 3 (A) miR-27a (HBC/Ctrl); (B) miR-27a (HBC/CHB); (C) miR-122 (CHB/Ctrl); (D) miR-122 (HBC/Ctrl); (E) miR-122 (HBC/CHB); and (F) miR-27a and miR-122 (HBC/CHB). [score:1]
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3
[+] score: 273
Other miRNAs from this paper: rno-mir-27b
Furthermore, inhibiting miR-27a elevated the expression level of PPARγ but downregulated TGF-β1, Smad3, CTGF, Fibronectin, and Collagen I expression by qRT-PCR (Figure 5C), Western blot (Figure 5D) and immunohistochemistry analyses (Figure 5E). [score:10]
Moreover, miR-27a mimics downregulated the expression of PPARγ but increased TGF-β1, Smad3, CTGF, Fibronectin, and Collagen I expression by qRT-PCR (Figure 6C), Western blot (Figure 6D) and immunohistochemistry analyses (Figure 6E). [score:8]
Moreover, we provide evidences that PPARγ, as a direct target of miR-27a, suppresses TGF-β1 -induced fibrosis through inactivating fibrosis-related gene expressions. [score:8]
Accordingly, miR-27a inhibition led to increased PPARγ expression but decreased expression of TGF-β1, Smad3, CTGF, Fibronectin, and Collagen I by qRT-PCR (Figure 2C) and Western blot analyses (Figure 2D). [score:7]
Requirement of PPARγ for the miR-27a antagonism effect on downstream gene expressions in vitroIn order to explore whether the effect of miR-27a on downstream gene expressions depended on PPARγ, cells were first treated with PPARγ siRNA and then with miR-27a inhibitor. [score:7]
Figure 8 MiR-27a inhibits PPARγ and aggravates tubulointerstitial fibrosis and progression of DN through activating TGF-β1/Smad3 signaling pathway and promoting the expression of CTGF, Fibronectin, and Collagen I. To investigate the effect of high glucose on the time course expression of miR-27a and downstream gene expressions, NRK-52E cells were cultured in different concentrations of glucose (5, 15 and 30 mM) for 12, 36 and 72 hours, respectively. [score:7]
We found that miR-27a directly targets PPARγ and promotes TGF-β1 -induced expression of profibrotic genes in DN. [score:6]
These results suggest that PPARγ, as a direct target of miR-27a, decreases fibrosis related gene expressions in vitro. [score:6]
Dysregulation of miR-27a has been reported in different diseases such as metabolic syndrome [24], diabetes [25, 26], obesity [27], and non-alcoholic fatty liver disease [28]. [score:6]
MiR-27a depletion upregulates PPARγ and inhibits fibrosis in vivoTo investigate the biological function of miR-27a in vivo, we administered miR-27a inhibitor to diabetic rats. [score:6]
MiR-27a inhibits PPARγ and aggravates tubulointerstitial fibrosis and progression of DN through activating TGF-β1/Smad3 signaling pathway and promoting the expression of CTGF, Fibronectin, and Collagen I. The present study demonstrates the significant role of miR-27a/PPARγ pathway in renal TIF in DN. [score:5]
Next, we examined whether the changes of miR-27a expression level modulated fibrosis-related downstream gene expressions. [score:5]
In order to explore whether the effect of miR-27a on downstream gene expressions depended on PPARγ, cells were first treated with PPARγ siRNA and then with miR-27a inhibitor. [score:5]
MiR-iNC: miRNA inhibitor negative control; miR-27ai: miR-27a inhibitor; miR-NC: miRNA negative control; miR-27am: miR-27a mimic; p-SMAD3, phospho-SMAD3; t-SMAD3, total-SMAD3. [score:5]
To further prove that miR-27a promotes PPARγ-mediate fibrosis in vitro, we examined the effect of miR-27a inhibitor and mimics on fibrosis-related downstream gene expressions in high glucose (30 mM) cultured NRK-52E cells. [score:5]
The predicted 3′-untranslated regions (UTR) sequence of PPARγ interacting with miR-27a and mutated sequences within the predicted target sites were synthesized and inserted into the pRL-TK control vector (Promega, Madison, WI, USA). [score:5]
Figure 4Requirement of PPARγ for the miR-27a antagonism effect on downstream gene expressions in vitro(A) MiR-27ai attenuated the silencing effect of PPARγ siRNA on TGF-β1 expression (immunofluorescence, scale bar 100 μm) and (B) quantification analysis. [score:5]
NG, normal glucose; HG, high glucose; p-SMAD3, phospho-SMAD3; t-SMAD3, total-SMAD3; miR-iNC: miRNA inhibitor negative control; miR-27ai: miR-27a inhibitor; wt: wild type; mt: mutant type. [score:5]
Targeting miR-27a might be an alternative to suppress renal TIF in DN and opens new avenues into novel therapeutic strategies. [score:5]
NC, normal control; DM, diabetes mellitus; DM_miR-iNC, diabetic rats treated with miRNA inhibitor negative control; DM_miR-27ai, diabetic rats treated with miR-27a inhibitor; p-SMAD3, phospho-SMAD3; t-SMAD3, total-SMAD3; MTS, Masson' s trichrome stain. [score:5]
However, when we treated PPARγ-silenced cells with miR-27a inhibitor, we found that the expression of PPARγ was restored. [score:5]
Figure 5MiR-27a inhibitor improves fibrosis in vivo(A) The miR-27a level was increased in the plasma and (B) kidney tissues of diabetic rats and decreased with miR-27a inhibition treatment. [score:5]
38 ± 3.23 [#] UAER (ug/min) 1.45 ± 0.210.67 ± 0.06 [#] UACR (ug/mmol) 27.32 ± 2.3215.35 ± 1.16 [#]Ccr (mL·min [−1]·Kg [−1]) 3.48 ± 0.457.37 ± 0.82 [#] DM_miR-iNC, diabetic rats treated with miRNA inhibitor negative control; DM_miR-27ai, diabetic rats treated with miR-27a inhibitor; Scr, serum creatinine; Serum BUN, serum blood urea nitrogen; Urinary NAG, urinary N-acetyl-β-D-glucosaminidase; UAER, urine albumin excretion rate; UACR, urine albumin to creatinine ratio; Ccr, creatinine clearance rate; * P < 0.01; # P < 0.001. [score:5]
MiR-27a inhibitor (miR-27ai), miR-27a mimics (miR-27am), or the appropriate negative controls (NC) of miRNA inhibitor (miR-iNC) and miRNA mimics (miR-NC), respectively, were purchased from GenePharma (Shanghai, China) and transfected at a final concentration of 50–100 nM in the cells using HiPerFect Transfection Reagent (Qiagen, Hilden, Germany) according to the manufacturer's recommendations. [score:5]
MiR-27a and miR-27b are negative regulatory factors of adipocytes and have been shown to directly target PPARγ [46, 47]. [score:5]
The results have shown that miR-27a inhibitor (miR-27ai) caused increased expression of PPARγ but decreased TGF-β1 as detected by immunofluorescence microscopy (Figure 2A and 2B). [score:5]
MiR-27a depletion upregulates PPARγ and inhibits fibrosis in vivo. [score:5]
NT: non -targeting; siRNA: small interfering RNA; miR-27ai: miR-27a inhibitor; p-SMAD3, phospho-SMAD3; t-SMAD3, total-SMAD3. [score:5]
These results suggest that miR-27a directly suppresses PPARγ and induces fibrosis in high glucose cultured NRK-52E cells in vitro. [score:4]
The miR-27 family, including miR-27a and miR-27b, has emerged as a new key regulator in the physiological processes of atherosclerosis [19] and cardiovascular disease [20]. [score:4]
By targeting PPARγ, miR-27a serves as an initiator in triggering a cascade of several pro-fibrotic mediators relevant in the development of fibrosis in DN. [score:4]
To further elucidate whether PPARγ is a direct target of miR-27a, we used a dual-luciferase reporter assay to detect whether miR-27a directly interacted with the 3′-UTR of PPARγ mRNA. [score:4]
Future studies are directed to explore the differential changes of miR-27a in DN patients with only large vascular complications versus patients without target organ damage. [score:4]
Figure 8 MiR-27a inhibits PPARγ and aggravates tubulointerstitial fibrosis and progression of DN through activating TGF-β1/Smad3 signaling pathway and promoting the expression of CTGF, Fibronectin, and Collagen I. (A) Increased plasma miR-27a level in DN patients (n = 30) compared with healthy normal controls (n = 30). [score:4]
NRK52E cells transfected with 120 ng miR-27a inhibitor or negative controls, followed by co-transfection with 30 ng of the wild-type or mutant 3′-UTR of PPARγ using 0.45 μL of Fugene (Promega, Madison, WI, USA). [score:3]
We found that miR-27a antagonized the expression of PPARγ and promoted TIF through the TGF-β1/Smad3 signaling. [score:3]
The mean value of miR-27a expression in glucose-free cultured cells was used as the calibrator. [score:3]
Figure 1High glucose promotes miR-27a and directly modulates PPARγ -induced fibrosis in vitro(A) High glucose (30 mM) stimulated miR-27a expression in a time -dependent manner compared between groups. [score:3]
Two groups with seven rats each were studied: diabetic rats treated with dimethyl sulphoxide (DMSO) and diabetic rats treated with miR-27a inhibitor or mimics. [score:3]
The mRNA level of miR-27a increased in the plasma (Figure 5A) and kidney tissues (Figure 5B) of diabetic rats but was decreased with miR-27a inhibition. [score:3]
Biological parameters for diabetic rats treated with miR-27a inhibitor at week 12. [score:3]
Correspondingly, TIF was improved in diabetic rats treated with miR-27a inhibitor as detected by Masson's trichrome stain and the quantification analysis (Figure 5F). [score:3]
Meanwhile, further studies are warranted to validate the significance of miR-27a in expanded samples of DN and also in other non-renal diseases. [score:3]
High glucose promotes miR-27a and fibrosis via repression of PPARγ in vitroTo investigate the effect of high glucose on the time course expression of miR-27a and downstream gene expressions, NRK-52E cells were cultured in different concentrations of glucose (5, 15 and 30 mM) for 12, 36 and 72 hours, respectively. [score:3]
We found that inhibition of miR-27a significantly decreased the level of serum creatinine (Scr), serum blood urea nitrogen (BUN), urinary N-acetyl-β-D-glucosaminidase (NAG), urine albumin excretion rate (UAER), urine albumin to creatinine ratio (UACR) and elevated creatinine clearance rate (Ccr) (Table 1). [score:3]
Previous studies have reported that miR-27a targets PPARγ in mediating inflammatory processes [21]. [score:3]
It was shown that miR-27a inhibitor led to a remarkable increase in the luciferase activity of wild-type 3′-UTR of PPARγ but not the mutant (Figure 1I and 1J). [score:3]
Furthermore, as illustrated by qRT-PCR (Figure 1E and 1G) and Western blot analyses (Figure 1F and 1H), with the increase of miR-27a, the expression level of PPARγ decreased, with concomitant increase in TGF-β1, phospho-Smad3, CTGF, Fibronectin, and Collagen I in a time and dose dependent manner. [score:3]
As detected by qRT-PCR, the expression level of miR-27a increased in a time and dose dependent manner, independent of the effect of mannitol (30 mM) (Figure 1A and 1B). [score:3]
Requirement of PPARγ for the miR-27a antagonism effect on downstream gene expressions in vitro. [score:3]
High glucose promotes miR-27a and directly modulates PPARγ -induced fibrosis in vitro. [score:2]
MiR-27a inhibitor improves fibrosis in vivo. [score:2]
A hypothetical mo del illustrating that miR-27a/PPARγ signaling regulated renal tubulointerstitial fibrosis through the TGF-β1/Smad3 mediated fibrosis in diabetic nephropathy. [score:2]
To investigate the biological function of miR-27a in vivo, we administered miR-27a inhibitor to diabetic rats. [score:1]
Pearson correlation analysis was used to analyze correlations between plasma miR-27a and biological parameters. [score:1]
NC, normal control; DM, diabete mellitus; DM_miR-NC, diabetic rats treated with miRNA negative control; DM_miR-27am, diabetic rats treated with miR-27a mimics; p-SMAD3, phospho-SMAD3; t-SMAD3, total-SMAD3; MTS, Masson' s trichrome stain. [score:1]
The mRNA level of miR-27a increased in the plasma (Figure 6A) and kidney tissues (Figure 6B) of diabetic rats and further increased with miR-27a mimics treatment. [score:1]
Interestingly, an increase in the levels of circulating miR-27a in patients with type 1 and type 2 diabetes has been recently reported [24, 26]. [score:1]
Collectively, the current results implicate miR-27a/PPARγ as an initiating mechanism triggering the process of renal TIF in DN by activating the TGF-β1/Smad3 signaling [43]. [score:1]
In contrast, miR-27a enrichment with miR-27a mimics (miR-27am) had the opposite effects (Figure 2E, 2F, 2G and 2H). [score:1]
The present study has demonstrated that plasma miR-27a is increased in DN and confers declined renal function. [score:1]
We treated diabetic rats with miR-27a mimics and found that the level of Scr, serum BUN, urinary NAG, UAER, UACR were significantly increased and Ccr was decreased (Table 2). [score:1]
These data further validate the in vitro and in vivo results that miR-27a confers unfavorable renal function and TIF through PPARγ -induced activation of the TGF-β1/Smad3 pathway. [score:1]
Elevated plasma miR-27a reflects unfavorable renal function and increased tubulointerstitial fibrosis in DN patients. [score:1]
High glucose promotes miR-27a and fibrosis via repression of PPARγ in vitro. [score:1]
These findings provide evidences that PPARγ is a critical intermediate modulator downstream of miR-27a. [score:1]
These data demonstrate that miR-27a, through repression of PPARγ, induces fibrosis in vitro. [score:1]
36 ± 7.35 [#] UAER (ug/min) 1.48 ± 0.252.85 ± 0.92 [#] UACR (ug/mmol) 25.65 ± 2.1858.67 ± 3.34 [#]Ccr (mL·min [−1]·Kg [−1]) 3.12 ± 0.340.68 ± 0.05 [#] DM_miR-NC, diabetic rats treated with miRNA mimics negative control; DM_miR-27am, diabetic rats treated with miR-27a mimics; Scr, serum creatinine; Serum BUN, serum blood urea nitrogen; Urinary NAG, urinary N-acetyl-β-D-glucosaminidase; UAER, urine albumin excretion rate; UACR, urine albumin to creatinine ratio; Ccr, creatinine clearance rate; * P < 0.01; # P < 0.001. [score:1]
Furthermore, the mRNA level of miR-27a increased in the serum of diabetic patients, accompanied by increased Scr, proteinuria, urinary NAG and decreased eGFR. [score:1]
In DN patients, the level of serum miR-27a was positively correlated with serum creatinine (Figure 7B), proteinuria (Figure 7C), urinary NAG (Figure 7D) and negatively with eGFR (Figure 7E). [score:1]
TIF was worsened in diabetic rats treated with miR-27a mimics as detected by Masson's trichrome stain and the quantification analysis (Figure 6F). [score:1]
In doing so, we could be able to find out the correlation between the level of miR-27a and the severity of DN. [score:1]
In conclusion, our data demonstrate a mechanism that the miR-27a/PPARγ pathway promotes TIF in DN through the TGF-β1/Smad3 pathway. [score:1]
These results suggest that in DN, miR-27a confers an unfavorable renal function and serum miR-27a might serve as an alternative approach to reflect the severity of renal tubulointerstitial fibrosis. [score:1]
Elevated plasma miR-27a reflects unfavorable renal function and increased tubulointerstitial fibrosis in patients with diabetic nephropathy. [score:1]
To explore the clinical significance of miR-27a in DN patients, we analyzed the correlation between serum miR-27a level with biological parameters of DN patients. [score:1]
To investigate the effect of miR-27a on renal tubulointerstitial fibrosis, miR-27a inhibitor or mimics (4 ng/mm [3]) was injected peritoneally to diabetic rats every day. [score:1]
Figure 6MiR-27a mimics aggravate fibrosis in vivo(A) The miR-27a level was increased in the plasma and (B) kidney tissues of diabetic rats and further increased treated with miR-27a mimics. [score:1]
In terms of the relationship between miR-27a and PPARγ in diabetes, we design the present study to delve into the role of miR-27a in the progression of diabetic DN. [score:1]
We also explored whether the miR-27a/PPARγ signaling promotes renal TIF in DN and the underlying mechanisms. [score:1]
A hypothetical mo del illustrated that miR-27a/PPARγ signaling promoted renal TIF through the TGF-β1/Smad3 -induced fibrosis in DN (Figure 8). [score:1]
Emerging data have shown that miR-27 plays important roles in lipid metabolism, inflammation, angiogenesis, adipogenesis, oxidative stress, renin-angiotensin system, insulin resistance and type 2 diabetes [21]. [score:1]
MiR-27a mimics promote fibrosis via PPARγ pathway in vivoWe treated diabetic rats with miR-27a mimics and found that the level of Scr, serum BUN, urinary NAG, UAER, UACR were significantly increased and Ccr was decreased (Table 2). [score:1]
We did not analyze the level of miR-27a in different stages of DN, which limited its clinical value in predicting the progression of DN. [score:1]
The mutant PPARγ binding site was generated in the complementary site for the seed region of miR-27a. [score:1]
Our current study demonstrates that miR-27a promotes renal TIF in DN through repression of PPARγ. [score:1]
Biological parameters for diabetic rats treated with miR-27a mimics at week 12. [score:1]
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Other miRNAs from this paper: rno-mir-27b, rno-mir-182
Moreover, miR-27a up-regulation could both inhibit adipogenesis and promote osteogenesis by directly targeting PPARγ and GREM1. [score:9]
Furthermore, osteogenesis -associated genes were significantly and differentially expressed in BMSCs from the miR-27a group: GREM1 was down-regulated, whereas Runx2 and Bmp-2 were up-regulated. [score:9]
Because miR-27a was down-regulated in the Mo del group while PPARγ and GREM1 were both up-regulated, we next performed a correlation analysis, which showed that PPARγ and GREM1 were both negatively correlated with miR-27a expression (Fig. 1g,h). [score:9]
showed that PPAR γ and GREM1 were down-regulated in the miR-27a mimics group and up-regulated in the miR-27a inhibitor group compared with the relevant control groups (Fig. 2b). [score:8]
Here, we found that miR-27a up-regulation enhanced osteogenic differentiation and suppressed adipogenic differentiation by inhibiting PPARγ and GREM1 in steroid -induced rat BMSCs. [score:8]
Indeed, we detected PPARγ up-regulation in the steroid -induced ONFH rat mo del and concomitant miR-27a down-regulation in the same femoral head tissue. [score:7]
miR-27a was down-regulated while PPARγ and GREM1 were up-regulated in the steroid -induced ONFH rat mo del. [score:7]
miR-27a was down-regulated, while PPARγ and GREM1 were up-regulated in the steroid -induced ONFH rat mo del. [score:7]
Corroborative results were obtained, showing that miR-27a was significantly down-regulated while miR-182 was obviously up-regulated in the Mo del group (Fig. 1c,d). [score:7]
Furthermore, GREM1 was significantly down-regulated in the miR-27a and si-GREM1 groups, whereas Runx2 and Bmp-2 were significantly up-regulated in the miR-27a group compared with the Mo del, si-PPARγ and si-GREM1 groups. [score:6]
Among the 37 differentiated expressed miRNAs, miR-27a was a down-regulated one, and subsequent bioinformatics and our previous studies showed that miR-27a was likely involved in the initiation of ONFH and had a close interaction with PPARγ and GREM1 as described before, this triggered us to further detect miR-27 and its role in ONFH. [score:6]
Furthermore, GREM1 was significantly down-regulated in the miR-27a and si-GREM1 groups, whereas Runx2 and Bmp-2 were significantly up-regulated in the miR-27a group compared with the Mo del, si-PPARγ and and si-GREM1 groups (Fig. 6c). [score:6]
Adipogenic differentiation was enhanced, osteogenic differentiation was inhibited and miR-27a was down-regulated in steroid -induced rat BMSCs. [score:6]
Adipogenic differentiation was enhanced, osteogenic differentiation was inhibited, and miR-27a was down-regulated in steroid -induced rat BMSCs. [score:6]
The RNA oligoribonucleotides (miR-27a mimics, miR-27a inhibitor, mimics control, inhibitor control, si-PPARγ, and si-GREM1) used in this study were synthesized by Shanghai GenePharma Co. [score:5]
The expression of PPARγ and GREM1 without 3′UTRs rescued the effects of miRNA-27a overexpression on adipogenic and osteogenic differentiation in steroid -induced rat BMSCs. [score:5]
These results showed that the expression of PPARγ and GREM1 without 3′UTRs could partially rescue the effects of miR-27a overexpression (Fig. 5c,d). [score:5]
org/) found that the PPAR γ and GREM1 mRNAs both contain a matching 3′ untranslated region (UTR) sequence that targets the seed region of miR-27a; these sequences are presented in Fig. 2a. [score:5]
These results show that by targeting both PPARγ and GREM1, miR-27a regulates BMSC differentiation in a combined manner and thus serves as a potent regulator of the balance between adipogenesis and osteogenesis. [score:5]
Expression of PPARγ and GREM1 without 3′UTRs partially rescued the effects of miRNA-27a overexpression on adipogenic and osteogenic differentiation in steroid -induced rat BMSCs. [score:5]
We next transfected rat BMSCs with miR-27a mimics, an miR-27a inhibitor, a mimics control or an inhibitor control to detect the interaction between miR-27a and PPAR γ and GREM1. [score:5]
Using Lipofectamine™ 2000 (Invitrogen, Carlsbad, CA, USA), the BMSCs were co -transfected with the miRNAs (miR-27a mimics, miR-27a inhibitor, mimics control or inhibitor control) and reporter vectors (wild-type or mutant-type). [score:5]
We next co -transfected rat BMSCs with PPARγ or GREM1 expression vectors that lacked the 3′UTR to further confirm miR-27a attenuates adipogenic differentiation and promotes osteogenic differentiation by targeting PPARγ and GREM1. [score:5]
miRNA-27a up-regulation had a stronger effect on the attenuation of adipogenic differentiation in steroid -induced rat BMSCs than si-PPARγ and si-GREM1. [score:4]
In particular, miR-27a was down-regulated in steroid -induced ONFH. [score:4]
miRNA-27a up-regulation attenuated adipogenic differentiation and promoted osteogenic differentiation in steroid -induced rat BMSCs. [score:4]
Overall, miR-27a up-regulation had a stronger effect on simultaneously attenuating adipogenic differentiation and promoting osteogenic differentiation in steroid -induced rat BMSCs than si-PPARγ and si-GREM1. [score:4]
miRNA-27a up-regulation had a stronger effect on attenuating adipogenic differentiation in steroid -induced rat BMSCs than si-PPARγ and si-GREM1. [score:4]
The western blotting and qRT-PCR results showed a significant reduction in PPARγ expression in the miR-27a and si-PPARγ groups compared with the Mo del and si-GREM1 groups, and lower expression of C/EBPα was observed in the miR-27a group than in the other groups. [score:4]
These results suggested that miR-27a up-regulation effectively attenuated adipogenic differentiation and promoted osteogenic differentiation in steroid -induced rat BMSCs. [score:4]
Hence, we identified miR-27a as a probable key regulator of adipogenesis in steroid -induced BMSCs and a potential therapeutic target for ONFH treatment. [score:4]
In addition, significantly enhanced luciferase activity was observed in BMSCs that were co -transfected with the miR-27a inhibitor and pmirGLO-wt-PPARγ compared with the cells that were co -transfected with the miR-27a inhibitor and pmirGLO-mt-PPARγ. [score:4]
These results indicate that miR-27a can bind to the pmirGLO-wt-PPARγ and pmirGLO-wt-GREM1 mRNAs and negatively regulate luciferase activity, implying that PPARγ and GREM1 are potential targets of miR-27a. [score:4]
PPARγ and GREM1 were direct targets of miRNA-27a. [score:4]
The qRT-PCR results confirmed successful transfection, with significantly higher miR-27a expression in the miR-27a group than in the Blank group (Fig. 4a). [score:3]
How to cite this article: Gu, C. et al. miR-27a attenuates adipogenesis and promotes osteogenesis in steroid -induced rat BMSCs by targeting PPARγ and GREM1. [score:3]
However, further studies on the detailed mechanisms and feasibility are still required before miR-27a can be targeted for clinical applications. [score:3]
A similar result was observed in BMSCs that were co -transfected with the miR-27a mimics and pmirGLO-wt-GREM1 or the cells that were co -transfected with the miR-27a inhibitor and pmirGLO-wt-GREM1. [score:3]
Moreover, the qRT-PCR results revealed that miR-27a was significantly down-regulated in BMSCs from the Mo del group compared with the Control group on day 7 and 14 (Fig. 3j). [score:3]
The miR-27a expression levels were assessed with qRT-PCR using an ABI 7500 thermal cycler and a High-Specificity miR-27a qRT-PCR Detection Kit (Stratagene Corp, La Jolla, CA, USA), according to the manufacturer’s instructions. [score:3]
The bioinformatics analysis suggested that PPARγ and GREM1 were potential target genes of miR-27a. [score:3]
Steroid -treated BMSCs were then separately transfected with pcDNA3.1-PPARγ, pcDNA3.1-GREM1, or the miR-27a mimics, or co -transfected with the expression vectors and miR-27a mimics. [score:3]
This result suggests that PPAR γ and GREM1 are potential target genes of miR-27a. [score:3]
A similar result was observed in BMSCs that were co -transfected with the miR-27a mimics and pmirGLO-wt-GREM1 or cells that were co -transfected with the miR-27a inhibitor and pmirGLO-wt-GREM1 (Fig. 2c,d). [score:3]
qRT-PCR was performed to determine the expression levels of miR-27a and miR-182, and to verify the microarray analysis. [score:3]
Compared with the siRNAs targeting PPARγ and GREM1, miR-27a showed a stronger effect on comprehensively regulating adipogenic and osteogenic differentiation. [score:3]
Correspondingly, the qRT-PCR and western blotting results showed that the expression of adipogenesis -associated genes (PPARγ and C/EBPα) was significantly reduced in BMSCs from the miR-27a group compared with the Mo del and the Scramble groups. [score:2]
This result is in accordance with our and strongly suggests that miR-27a is involved in the biological processes of adipogenesis and osteogenesis in steroid -induced rat BMSCs. [score:1]
Because the differentiation of cultured BMSCs can simulate homeostasis of cell fate determination in vivo, we was further examined miR-27a function in BMSCs isolated from rats by transfecting BMSCs with miR-27a mimics using Lipofectamine™ 2000 (specified in the following part). [score:1]
Cell cultures from the Mo del group, Scramble group, and miR-27a group were terminated on day 14 after dexamethasone administration. [score:1]
We transfected rat BMSCs with miR-27a, si-PPARγ, and si-GREM1 to compare the efficacy of miR-27a, si-PPARγ, and si-GREM1 on adipogenic and osteogenic differentiation. [score:1]
We generated rat BMSCs that overexpressed miR-27a (miR-27a group) to investigate the involvement of miR-27a in adipogenesis and osteogenesis. [score:1]
On day 14 of steroid treatment, revealed a greater number of BMSCs that were stained blue/purple in the miR-27a group in the Mo del, si-PPARγ and si-GREM1 groups (Fig. 5d). [score:1]
U6 small nuclear RNA (snRNA) was used as the internal reference for normalization of the miR-27a levels. [score:1]
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In accordance with the decreased TICAM-2 expression, increased miR-27a levels induced by intrathecal injection of mimic-27a also prevented the increases in TLR [4] and nuclear NF-κB p65 expression, as well as the increased IL-1β levels, whereas suppression of miR-27a by treatment with AMO-27a reversed the above changes, indicating that the TLR [4]/NF-κB/IL-1β pathway is involved in the miR-27a -mediated regulation of inflammation in the spinal cord through TICAM-2 targeting. [score:10]
Intrathecal pretreatment with an miR-27a mimic and anti-miR oligonucleotides successfully regulated TICAM-2 expression after ischemia reperfusionTo explore the effects of a synthetic miR-27a mimic (mimic-27a), miR-27a AMO (AMO-27a), and a negative control mRNA (NC-27a) on TICAM-2 expression in the spinal cord after IR, we intrathecally injected mimic-27a, AMO-27a, and NC-27a for three days before ischemia, and then examined both the mRNA and protein expression of TICAM-2 by RT-PCR and western blotting, respectively. [score:8]
Consistent with this, here, we observe that TLR [4] expression is also significantly upregulated when TICAM-2 expression increased and miR-27a decreased at both 24 and 72 hours after IR (Figure  4a, b, c, d, e). [score:8]
miR-27a upregulation attenuates IR -induced inflammatory damage to the BSCB by negatively regulating TICAM-2 of the TLR [4] signaling pathway and inhibiting the NF-κB/IL-1β pathway. [score:7]
On the other hand, some studies showed an upregulation of miR-27a for systemic inflammation, instead of the down-regulation as described in this study in the event of systemic inflammation [28, 39]. [score:7]
Our in vivo data, shown in Figure  4a, b, c, are in close accordance with previous studies, showing that compensating for decreased miR-27a levels by continuous intrathecal injection of mimic-27a into the subarachnoid space of IR mo del rats, reduced the mRNA and protein expression of TICAM-2 by inhibiting the translation and/or promoting the degradation of its mRNA. [score:7]
These disagreements might be caused by the different observation time points, which are consistent with the descriptions of that no changes being observed in miR-27a expression for at 6 hours, instead of downregulation for at 24 hours after lipopolysaccharide (LPS) treatments [28]. [score:6]
Intrathecal pretreatment with mimic-27a inhibited TLR [4]/NF-κB/IL-1β activation after ischemia reperfusionTo further confirm that miR-27a is involved in TLR [4] activation by regulating the expression of TICAM-2 after IR, we examined the mRNA and protein levels of TLR [4], NF-κB, and the downstream inflammatory cytokine IL-1β by ELISA. [score:6]
Taken together, we identify TICAM-2 as a novel target of miR-27a and show that downregulation of miR-27a promotes IR -induced inflammatory damage to the BSCB by facilitating activation of the TLR [4]/NF-κB/IL-1β signaling pathway. [score:6]
An Iinjection of mimic-27a attenuated BSCB dysfunction, which was manifested as reduced fluorescent dye and EB extravasation, and was suppressed by the injection of AMO-27a; this finding indicatesd that miR-27a regulates inflammatory damage to the BSCB by targeting the TICAM-2 mRNA and the TLR [4]/NF-κB/IL-1β pathway. [score:6]
These results are consistent with the hypothesis that the IR -mediated reduction in miR-27a down-regulates TICAM-2 expression, which in turn influences TLR [4] signaling and the activation of downstream inflammatory cytokines. [score:6]
Our results demonstrated that increasing the expression of miR-27a attenuated IR -induced spinal cord injury by negatively modulating the TLR [4] signaling regulator TICAM-2, which may be a new therapeutic target under neuroinflammatory conditions. [score:6]
Among the miRs identified, we observed that miR-27a was one of the most dysregulated miRs, and further defined TICAM-2, a key regulator of the TLR [4] pathway, as its target. [score:5]
Among them, miR-27a-3p, let-7a-5p, miR-10b-5p, and miR-23b-3p have been shown to function as regulators of spinal cord development and remo deling, and have been implicated in diseases of the spinal cord [20, 21]. [score:5]
In addition, searching the TargetScanHuman 6.2 and MicroCosm Targets version 5databases revealed a perfect match to a miR-27a binding site in the 3′-UTR of the TICAM-2 gene (Figure  3a), which was confirmed by quantitative real-timeq RT-PCR (Figure  3b). [score:5]
Therefore, we hypothesized that downregulation of miR-27a might play a role in mediating TLR [4] -mediated secondary inflammatory damage after IR by up -regulating the TICAM-2 transcript. [score:5]
To explore the effects of a synthetic miR-27a mimic (mimic-27a), miR-27a AMO (AMO-27a), and a negative control mRNA (NC-27a) on TICAM-2 expression in the spinal cord after IR, we intrathecally injected mimic-27a, AMO-27a, and NC-27a for three days before ischemia, and then examined both the mRNA and protein expression of TICAM-2 by RT-PCR and western blotting, respectively. [score:5]
Further in vitro and in vivo studies still need to be conducted to identify the correlation between miR-27a and the corresponding target genes in the mode of inflammatory or anti-inflammatory actions to better elucidate the mechanism and provide potential therapeutic targets for IR. [score:5]
Among all the significantly changed miRs, miR-27a was the most significantly downregulated in injured spinal cords at the abovementioned time points. [score:4]
Intrathecal pretreatment with an miR-27a mimic and anti-miR oligonucleotides successfully regulated TICAM-2 expression after ischemia reperfusion. [score:4]
However, no obvious changes were detected when mo del animals were pretreated with NC-27a, suggesting that miR-27a directly modulates TICAM-2 expression i n vivo, and that modulation of miR-27a is particularly important in the pathophysiology of IR. [score:4]
For example, in the recsent study of Young et al. showed the opposite role of miR-27a in the regulation of vascular leaking by targeting vascular endothelium (VE)-cadherin in the endothelium [38]. [score:4]
To further confirm that miR-27a is involved in TLR [4] activation by regulating the expression of TICAM-2 after IR, we examined the mRNA and protein levels of TLR [4], NF-κB, and the downstream inflammatory cytokine IL-1β by ELISA. [score:4]
To the best of our knowledge, this is the first study to document a miR-27a target related to the TLR [4] pathway in spinal cord IR injury. [score:3]
The results showed that miR-27a was expressed at significantly low levels after IR and continuously decreased with time (P < 0.05, versus the sham group). [score:3]
We focused on miR-27a, which is predicted to contain sequences complementary to the 3'-untranslated region (UTR) of Toll-like receptor adaptor molecule 2 (TICAM-2). [score:3]
The profiles of TICAM-2 were expressed in an opposite manner as those of miR-27a. [score:3]
Given this, many target genes of miR-27a have been identified, some of which were showed to participated in innate immune response and inflammatory responses [28- 31]. [score:3]
Whether miR-27a specifically target TICAM-2 in vivo remainsed to be tested. [score:3]
Our present study provides clear evidence for the protective effects of specifically increasing miR-27a expression. [score:3]
We identified TICAM-2 as a novel target of miR-27a. [score:3]
Nine of the miRs (miR-200b-3p, miR-27a-3p, let-7a-5p, miR-21-5p, miR-10b-5p, miR-23b-3p, miR-221-3p, miR-100-5p, and miR-28-5p) were differently expressed at both 24 and 72 hours after reperfusion. [score:3]
The relative expression of miR-27a was normalized to U6. [score:3]
Figure 3 A putative target site of miR-27a located in the 3′-UTR of TICAM-2 mRNA was predicted by bioinformatics analysis. [score:3]
In this study, using a miRs microarray screening approach, we found that miR-27a expression was significantly altered at both 24 h and 72 hours after IR, and such results were as confirmed by qRT-qPCR (Figure  2). [score:3]
To analyze the specificity and efficacy of the miR-27a and AMO-27a, real-time PCR was performed as described above. [score:1]
Then, the effects of miR-27a were assessed in a rat mo del of IR by intrathecal pretreatment with an miR mimic and an anti-miR oligonucleotide (AMO) starting three days before ischemia. [score:1]
Increasing the levels of miR-27a by intrathecal pretreatment with mimic-27a significantly decreased TICAM-2 immunoreactivity after IR and the number of TICAM-2-TLR [4] positive cells, whereas these effects were reversed by intrathecal injection of AMO-27a. [score:1]
We intrathecally infused 100 μL of a synthetic miR-27a mimic (mimic-27a), an AMO (AMO-27a), or the negative control (NC-27a, all at 50 mg/kg; Jima Inc. [score:1]
The method used to pretreat rats with a mimic and an AMO of miRNA-27a (GenBank number: [NR_031833.1]) and negative controls has been previously described [17]. [score:1]
[1 to 20 of 40 sentences]
6
[+] score: 133
Other miRNAs from this paper: rno-mir-130b, rno-mir-146a, rno-mir-200a, rno-mir-182
The finding that miR-27a targets PPAR γ and controls the expression of β-catenin target genes provides novel and mechanistic insights into how miRNAs contribute to the development and progression of DN. [score:8]
It is also possible that by targeting miR-27a alone, β-catenin and TGF- β 45, 46, 47, 48 downstream events may be inhibited. [score:5]
We finally asked whether miR-27a -induced downstream changes depended on PPAR γ. Of note, the luciferase activity of wild-type 3′-UTR of PPAR γ was significantly increased when treated with miR-27a inhibitor (miR-27ai) but decreased with miR-27a mimics (miR-27am) as compared with the mutant (Figure 1i), indicating that PPAR γ is a direct downstream target of miR-27a. [score:5]
[26] The similarities and differences between our present study and the above studies are as follows: (1) by targeting PPAR γ, miR-27a could initiate each individual event provoking different downstream signalings in different cell types in diabetic kidney, which may have amplifying effects in exacerbating the disease; (2) miR-27a could contribute to the formation of the most typical pathological hallmark of diabetic glomerular lesions, for example, extracellular matrix accumulation and podocyte foot process effacement; and (3) miR-27a is a robust biomarker in DN, which may be used for evaluating the disease severity. [score:5]
Expression patterns of miR-27a and PPAR γ/β-catenin-related markers in renal biopsies from DN patientsWe verified the expression patterns of miR-27a and PPAR γ/β-catenin-related markers in human renal biopsy samples from DN patients. [score:5]
In addition, miR-27a upregulation has also been detected in animal mo dels of diabetes and DN patients. [score:4]
The results in this study, for the first time, demonstrate that miR-27a/PPAR γ axis, as an upstream regulatory signaling, dictates the expression of genes associated with podocyte biology via β-catenin pathway. [score:4]
First, miR-27a directly targets the 3′-UTR of PPARγ mRNA and provokes the PPAR γ -mediated downstream events (Figure 1). [score:4]
MiR-27a promotes podocyte injury via PPAR γ -mediated β-catenin activation in high glucoseHaving discovered the upregulation of miR-27a in high glucose condition, we next explored the underlying mechanisms of miR-27a -induced podocyte injury. [score:4]
Having discovered the upregulation of miR-27a in high glucose condition, we next explored the underlying mechanisms of miR-27a -induced podocyte injury. [score:4]
42, 43 It is also consistent with our previous study illustrating the inhibitory effect of miR-27a/PPAR γ axis in renal tubulointerstitial fibrosis in DN. [score:3]
Six groups of rats were used: (1) normal control (NC, n=6), (2) diabetic control (DM, n=7), (3) diabetic rats treated with NC miRNA inhibitor (DM_miR-iNC, n=8), (4) diabetic rats treated with miR-27ai (DM_miR-27ai, n=7), (5) diabetic rats treated with NC miRNA mimic (DM_miR-NC, n=6) and (6) diabetic rats treated with miR-27a mimic (DM_miR-27am, n=6). [score:3]
[38] In this study, we have identified that high glucose induces the expression of miR-27a in cultured podocytes. [score:3]
Then, we examined whether miR-27a modulated PPAR γ -mediated downstream gene expression levels in high glucose. [score:3]
More broadly, the potential of ‘partial agonists' to modulate protein phosphorylation may be feasible, possibly allowing for identification of novel miR-27a targeted drugs. [score:3]
Expression patterns of miR-27a and PPAR γ/β-catenin-related markers in renal biopsies from DN patients. [score:3]
We verified the expression patterns of miR-27a and PPAR γ/β-catenin-related markers in human renal biopsy samples from DN patients. [score:3]
Similar to changes detected in animal studies, compared with healthy transplant donor kidney biopsies, ISH analysis shows that miR-27a level was upregulated in podocytes of renal biopsies from DN patients (Figures 6a and b). [score:3]
The mean value of miR-27a expression in glucose-free cultured cells was used as the calibrator. [score:3]
These results indicate a correlation between miR-27a and PPAR γ -mediated downstream gene expression levels in high glucose cultured podocytes. [score:3]
Compared with normal control rats, miR-27a was upregulated in podocytes of diabetic rat kidney tissues, as well as in renal tubular epithelial cells, which was significantly abolished by miR-27ai and enriched by miR-27am (Figures 4a and b). [score:3]
The predicted 3′-UTRs sequence of PPAR γ interacting with miR-27a and mutated sequences within the predicted target sites were synthesized and inserted into the pRL-TK control vector (Promega, Madison, WI, USA). [score:3]
High glucose induces miR-27a expression in cultured podocytes. [score:3]
To confirm the localization of miR-27a in glomeruli, we next examined miR-27a expression using in situ hybridization (ISH). [score:3]
[44] In glomerular mesangial cells, miR-27a has been reported to induce progression of DN by targeting PPAR γ. [score:3]
As shown in Figure 2a, miR-27ai decreased miR-27a expression in podocytes by qRT-PCR analysis. [score:3]
Therefore, it raises the topic of combinational therapy in DN in that by synergistically targeting miR-27a/PPAR γ/β-catenin and miR-27a/PPAR γ/TGF- β signalings, both podocyte injuries and tubulointerstitial fibrosis could be reversed or even prevented. [score:3]
The therapeutic efficacy of miR-27a blockage by its inhibitors results in reversal of the mesenchymal transition and architectural defects of the podocyte. [score:3]
Parameters for diabetic rats treated with miR-27a inhibitor at week 12. [score:3]
This notion inspires us to develop new combinational therapeutic strategies to simultaneously regulate miR-27a downstream signaling, such as PPAR γ and β-catenin. [score:2]
miR-27a ISH. [score:1]
These data collectively demonstrate that miR-27a, via activation of PPAR γ/β-catenin signaling, induces high glucose cultured podocytes to undergo mesenchymal transition and apoptosis, hence incurring podocyte injury. [score:1]
ISH for miR-27a (50 nM) was performed as described previously. [score:1]
In addition, whether cross-talks between glomerular and tubular cells or cross-talks between podocytes and mesangial cells initiate miR-27a -mediated downstream signalings remains unknown at these stage. [score:1]
Having shown a reciprocal interplay between miR-27a and PPAR γ, we next investigated whether the effect of miR-27a on downstream gene expression levels and podocyte functions depended on PPARγ. [score:1]
Next, we investigated the effect of time and glucose concentration on miR-27a expression. [score:1]
Another intriguing finding in this study is that miR-27a -induced β-catenin activation depends on PPAR γ phosphorylation in DN. [score:1]
These results together suggest that miR-27a induces podocyte injury via the PPAR γ/β-catenin signaling. [score:1]
Third, miR-27a disrupts podocyte architectural integrity and reduces podocyte number in diabetic rats. [score:1]
Collectively, these results suggest that PPARγ is required in miR-27a -induced β-catenin activation and podocyte injury in high glucose. [score:1]
First, the level of miR-27a was increased in high glucose (30 mM) cultured podocytes as determined by quantitative real-time RT-PCR (qRT-PCR) analysis (Figure 1a). [score:1]
Parameters for diabetic rats treated with miR-27a mimics at week 12. [score:1]
In contrast, miR-27a enrichment with miR-27am had the opposite effects (Supplementary Figures 1a–f). [score:1]
The most novel finding in this study is that in DN miR-27a induces podocyte injuries and worsens renal function via PPAR γ -mediated β-catenin activation. [score:1]
Given that miR-27a induces abolishment of slit diaphragm -associated protein synaptopodin, we next examined whether miR-27a affected podocyte number and architectural integrity. [score:1]
In summary, we have shown that miR-27a, via activating PPAR γ/β-catenin signaling, exacerbates podocyte injury as evidenced by increased capacity of migration, invasion and apoptosis. [score:1]
This finding highlights the significance of miR-27a in podocyte pathophysiology in DN. [score:1]
We found that miR-27a was increased in a time -dependent (Figure 1c) and dose -dependent (Figure 1d) manner as detected by qRT-PCR. [score:1]
A hypothetical mo del illustrated that miR-27a, via PPAR γ -mediated β-catenin activation, promotes podocyte injury in DN (Figure 6k). [score:1]
This study provides a mechanistic interplay between miR-27a and PPAR γ/β-catenin activation in the pathogenesis of DN. [score:1]
To investigate the effect of high glucose stimulation on the expression of miR-27a and downstream genes, podocytes were cultured in different conditions and biological behaviors were observed. [score:1]
Further, elevated miR-27a level was found in microdissected glomeruli (Figure 4e) and plasma samples (Figure 4f) of diabetic rats, which was decreased by treatment with miR-27ai and increased by miR-27am. [score:1]
Finally, miR-27a deteriorates renal function as revealed by elevated albuminuria and dropped Ccr in diabetic rats. [score:1]
Next, we asked whether miR-27a-dictated podocyte injury depended upon the interplay between PPAR γ and β-catenin activation. [score:1]
These data further illustrate the functional interplay between miR-27a and PPAR γ/β-catenin signaling in diabetic rats in vivo. [score:1]
Thus, miR-27a/PPAR γ and β-catenin are intimately connected to constitute a pathologic axis having a crucial role in the pathogenesis of DN. [score:1]
[1 to 20 of 56 sentences]
7
[+] score: 105
Other miRNAs from this paper: mmu-mir-30a, mmu-mir-101a, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-132, mmu-mir-134, mmu-mir-135a-1, mmu-mir-138-2, mmu-mir-142a, mmu-mir-150, mmu-mir-154, mmu-mir-182, mmu-mir-183, mmu-mir-24-1, mmu-mir-194-1, mmu-mir-200b, mmu-mir-122, mmu-mir-296, mmu-mir-21a, mmu-mir-27a, mmu-mir-92a-2, mmu-mir-96, rno-mir-322-1, mmu-mir-322, rno-mir-330, mmu-mir-330, rno-mir-339, mmu-mir-339, rno-mir-342, mmu-mir-342, rno-mir-135b, mmu-mir-135b, mmu-mir-19a, mmu-mir-100, mmu-mir-139, mmu-mir-212, mmu-mir-181a-1, mmu-mir-214, mmu-mir-224, mmu-mir-135a-2, mmu-mir-92a-1, mmu-mir-138-1, mmu-mir-181b-1, mmu-mir-125b-1, mmu-mir-194-2, mmu-mir-377, mmu-mir-383, mmu-mir-181b-2, rno-mir-19a, rno-mir-21, rno-mir-24-1, rno-mir-30a, rno-mir-92a-1, rno-mir-92a-2, rno-mir-96, rno-mir-100, rno-mir-101a, rno-mir-122, rno-mir-125a, rno-mir-125b-1, rno-mir-125b-2, rno-mir-132, rno-mir-134, rno-mir-135a, rno-mir-138-2, rno-mir-138-1, rno-mir-139, rno-mir-142, rno-mir-150, rno-mir-154, rno-mir-181b-1, rno-mir-181b-2, rno-mir-183, rno-mir-194-1, rno-mir-194-2, rno-mir-200b, rno-mir-212, rno-mir-181a-1, rno-mir-214, rno-mir-296, mmu-mir-376b, mmu-mir-370, mmu-mir-433, rno-mir-433, mmu-mir-466a, rno-mir-383, rno-mir-224, mmu-mir-483, rno-mir-483, rno-mir-370, rno-mir-377, mmu-mir-542, rno-mir-542-1, mmu-mir-494, mmu-mir-20b, mmu-mir-503, rno-mir-494, rno-mir-376b, rno-mir-20b, rno-mir-503-1, mmu-mir-1224, mmu-mir-551b, mmu-mir-672, mmu-mir-455, mmu-mir-490, 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-504, mmu-mir-466d, mmu-mir-872, mmu-mir-877, rno-mir-466b-1, rno-mir-466b-2, rno-mir-466c, rno-mir-872, rno-mir-877, rno-mir-182, rno-mir-455, rno-mir-672, mmu-mir-466l, mmu-mir-466i, mmu-mir-466f-4, mmu-mir-466k, mmu-mir-466j, rno-mir-551b, rno-mir-490, rno-mir-1224, rno-mir-504, mmu-mir-466m, mmu-mir-466o, mmu-mir-466c-2, mmu-mir-466b-4, mmu-mir-466b-5, mmu-mir-466b-6, mmu-mir-466b-7, mmu-mir-466p, mmu-mir-466n, mmu-mir-466b-8, rno-mir-466d, mmu-mir-466q, mmu-mir-21b, mmu-mir-21c, mmu-mir-142b, mmu-mir-466c-3, rno-mir-322-2, rno-mir-503-2, rno-mir-466b-3, rno-mir-466b-4, rno-mir-542-2, rno-mir-542-3
DEX treatment up-regulated the expression of miRNA-483, miRNA-181a-1, miRNA-490 and miRNA-181b-1, while it down-regulated the levels of miR-122, miR-466b, miR-200b, miR-877, miR-296, miRNA-27a and precursor of miR-504. [score:9]
ACTH up-regulated the expression of miRNA-212, miRNA-182, miRNA-183, miRNA-132, and miRNA-96 and down-regulated the levels of miRNA-466b, miRNA-214, miRNA-503, and miRNA-27a. [score:9]
Both ACTH and 17α-E2 up-regulated the expression of miRNA-212, miRNA-132, miRNA-154, miRNA-494, miRNA-872, miRNA-194, and miRNA-24-1, but reduced the expression of miRNA-322, miRNA-20b, miRNA-339, miRNA-27a, miRNA-551b, and miRNA-1224. [score:8]
Real-time PCR (qRT-PCR) measurements demonstrated that ACTH treatment upregulated the expression of miRNA-212, miRNA-183, miRNA-182, miRNA-132 and miRNA-96, while down -regulating the expression of miRNA-466b, miRNA-214, miRNA-503 and miRNA-27a. [score:7]
Real-time quantitative PCR measurements confirmed that the expression of miR-212, miRNA-183, miRNA-182, miRNA-132, miRNA-370, miRNA-377 and miRNA-96 was up-regulated and that of miRNA-122, miRNA-200b, miRNA-466b, miRNA-138, miRNA-214, miRNA-503 and miRNA-27a down-regulated in adrenals from 17α-E2 treated rats. [score:7]
qRT-PCR measurements confirmed that the expression of miR-212, miRNA-183, miRNA-182, miRNA-132, miRNA-370, miRNA-377 and miRNA-96 was up-regulated and that of miRNA-122, miRNA-200b, miRNA-466b, miRNA-138, miRNA-214, miRNA-503 and miRNA-27a down-regulated in adrenals from 17α-E2 treated rats (Fig. 3 ). [score:7]
The levels of miR-212, miRNA-183, miRNA-182, miRNA-132, miRNA-370, miRNA-377, and miRNA-96 were up-regulated, whereas miR-125b, miRNA-200b, miR-122, miRNA-466b, miR-138, miRNA-214, miRNA-503 and miRNA27a were down-regulated in response to 17α-E2 treatment. [score:7]
Bt [2]cAMP stimulation of granulosa cells caused down-regulation of a majority of miRNAs, including miRNA-200b, miRNA-466b, miRNA-27a, miRNA-214, miRNA-138 and miRNA-19a, but expression levels of miRNA-212, miRNA-183, miRNA-182, and miRNA-132 were significantly increased. [score:6]
Expression of miRNA-27a (1.32-fold) was also down-regulated by DEX. [score:6]
Using qRT-PCR, we confirmed the down-regulation of miRNA-200b, miR-122, miR-19a, miRNA-466b, and miRNA-27a expression (Fig. 3 ). [score:6]
qRT-PCR measurements indicated that exposure of primary rat granulosa cells to Bt [2]cAMP for 24 h inhibited the expression of miRNA-200b, miRNA-466b, miRNA-27a, miRNA-214, and miRNA-138 and miRNA-19a while enhancing the expression of miRNA-212, miRNA-183, miRNA-182, and miRNA-132 (Fig. 4 ). [score:5]
Significant expression was also observed for miRNA-27a, miRNA-132 and miRNA-214, whereas very low expression was noted for all of the remaining (seven) miRNAs. [score:5]
The levels of miR-27a and miR-551b were down-regulated by all three hormones, ACTH, 17α-E2 and DEX. [score:4]
Significant ACTH -induced down-regulation of miRNA-466b, miRNA-214, miRNA-503 and miRNA-27a was also observed (Fig. 3 ). [score:4]
Finally the expression levels of miRNA-27a and miRNA-551b were significantly reduced in adrenals of ACTH, 17α-E2 or DEX treated animals. [score:3]
More specifically, we assessed the impact of Bt [2]cAMP treatment on the expression of miRNA-212, miRNA-122, miRNA-27a, miRNA-466b, miRNA-200b, miRNA-138, miRNA-214, miRNA-183, miRNA-182, miRNA-132, miRNA-96 and miRNA-19a. [score:3]
We next evaluated the effects of Bt [2]cAMP stimulation of rat ovarian granulosa cells and of mouse MLTC-1 Leydig tumor cells on the expression of twelve miRNAs (miRNA-212, miRNA-122, miRNA-183, miRNA-200b, miRNA-466b, miRNA-182, miRNA-96, miRNA-27a, miRNA-132, miRNA-214, miRNA-138 and miRNA-19a) whose adrenal expression was differentially altered in response to treatment of rats with ACTH, 17α-E2 or DEX. [score:3]
Furthermore, such DEX alteration of adrenal miRNA levels demonstrates that DEX suppression of endogenous ACTH secretion modulates a set of adrenal miRNAs, with the exception of miRNA-96, miRNA-466, and miRNA-27a, that are distinct from those modulated by treatment with exogenous ACTH. [score:3]
Dexamethasone treatment decreased miRNA-200b, miR-122, miR-19a, miRNA-466b and miRNA27a levels, but increased miRNA-183 levels. [score:1]
Quantitative RT-PCR (qRT-PCR) validation of miRNA-212, miRNA-200b, miRNA-183, miRNA-122, miRNA-19a, miRNA-466b, miRNA-182, miRNA-132, miRNA-138, miRNA-370, miRNA-96, miRNA-503, miRNA-27a and miRNA-214 levels in control, ACTH-, 17α-E2 or DEX -treated adrenals in vivo. [score:1]
0078040.g003 Figure 3Quantitative RT-PCR (qRT-PCR) validation of miRNA-212, miRNA-200b, miRNA-183, miRNA-122, miRNA-19a, miRNA-466b, miRNA-182, miRNA-132, miRNA-138, miRNA-370, miRNA-96, miRNA-503, miRNA-27a and miRNA-214 levels in control, ACTH-, 17α-E2 or DEX -treated adrenals in vivo. [score:1]
[1 to 20 of 21 sentences]
8
[+] score: 103
Other miRNAs from this paper: rno-mir-19b-1, rno-mir-19b-2, rno-mir-19a, rno-mir-217
ECs were transfected with miR-27a mimics or inhibitor, and GRK6 -targeting siRNA or GRK6 overexpression lentivirus (Lv-GRK6) for 48 h. miR-27a mimics promoted the EC proliferation, whereas the inhibitor reduced EC proliferation (Fig. 5a and b). [score:9]
We also found that GRK6, the direct target of miR-27a, participated in the regulation of secreted miR-27a from VSMCs on the proliferation of ECs in hypertension. [score:5]
The miR-27a mimics decreased the expression of GRK6, whereas the inhibitor had the opposite effect (Fig. 3d). [score:5]
org/)] were used, and four miRs (i. e., miR-19a, miR-19b, miR-27a, and miR-217) were predicted to target the 3′-untranslated region (3′ UTR) of GRK6 according to the score (the sequence comparison is shown in Supplementary Fig. S3a). [score:5]
The antagomiR-27a injection significantly decreased the expression of miR-27a in the left CCA (Fig. 6a) and increased the expression of GRK6 in ECs (Fig. 6b). [score:5]
These results suggested that the upregulation of miR-27a was the result of the increased exogenous mature miR-27a carried in the VSMC-MPs, rather than of the processing of endogenous precursor miR-27a. [score:4]
Compared with VSMC-MPs from 5% cyclic stretch, VSMC-MPs from 15% cyclic stretch showed significantly increased expression of mature miR-27a in the ECs (Fig. 4a), but there was no significant change in the expression of pre-miR-27a (Fig. 4b). [score:4]
The 15% cyclic stretch treatment increased the miR-27a level in VSMC-MPs, which directly targeted GRK6. [score:4]
Mimics of these four miRs were transfected into ECs, and the results showed that miR-27a and miR-217 regulated the expression of GRK6 (Supplementary Fig. S3b). [score:4]
The sequence of the rno-miR-27a inhibitor was 5′-GCG GAA CUU AGC CAC UGU GAA-3′. [score:3]
To confirm the transfer of miR-27a from VSMCs to ECs, VSMC-MPs from VSMCs exposed to different cyclic stretch protocols were used to treat ECs as described above, and the expression of mature miR-27a and precursor miR-27a (pre-miR-27a) in ECs was detected. [score:3]
Pathologically elevated cyclic stretch increased the secretion of miR-27a, which was transferred from VSMCs to ECs via the VSMC-MPs, subsequently targeted GRK6, and induced EC proliferation. [score:3]
These results suggest that miR-27a is transferred from VSMCs to ECs via VSMC-MPs and then decreases the expression of GRK6 in ECs. [score:3]
The role of miR-27a in the repression of GRK6 in ECs was demonstrated by transfecting mimics and inhibitor of miR-27a at a concentration of 100 nmol/L. [score:3]
Then, the existence and expression level of miR-27a and miR-217 in VSMC-MPs induced by different cyclic stretch protocols were determined. [score:3]
Our results revealed not only the mechanism of secreted miR-27a by which hypertension regulates EC functions, but also a novel therapeutic approach to attenuate the abnormal proliferation of ECs in hypertension. [score:2]
To conclude, as shown in Fig. 7, the present study revealed that pathologically increased cyclic stretch increased the secretion of miR-27a from VSMCs via VSMC-MPs. [score:1]
B-miR-27a in the VSMCs and ECs was tracked using rhodamine-labeled streptavidin and detected by immunofluorescence. [score:1]
Biotinylated miR-27a (B-miR-27a, synthesized by RiboBio) was transfected into VSMCs using Lipofectamine [TM] 2000 (Invitrogen) at a concentration of 30 nmol/L, and the culture media was exchanged 6–8 h after transfection to remove the free B-miR-27a. [score:1]
miR-27a tracing. [score:1]
The effect of miR-27a was further validated by the response of a GRK6 3′ UTR reporter to the miR-27a mimics in HEK 293 T cells. [score:1]
miR-27a was transferred from VSMCs to ECs via VSMC-MPs. [score:1]
Level of miR-27a in VSMC-MPs was detected by. [score:1]
Therefore, locally decreasing miR-27a could be a novel therapeutic approach to attenuate the abnormal proliferation of ECs that occurs in hypertension. [score:1]
Decreasing miR-27a levels in vivo attenuated the abnormal EC proliferation during hypertension. [score:1]
Treatment of ECs with the VSMC-MPs from VSMCs transfected with B-miR-27a resulted in the presence of B-miR-27a in ECs (Fig. 4c). [score:1]
These results indicate that high cyclic stretch caused by hypertension induces the secretion of miR-27a via VSMC-MPs. [score:1]
Ovchinnikova et al. found that the level of circulating miR-27a was lower in acute heart failure patients with early decreases in renal function 36. [score:1]
Therefore, the effects of miR-27a and GRK6 on EC proliferation were examined. [score:1]
The above results indicate that high cyclic stretch increases the level of miR-27a in VSMC-MPs, and the miR-27a is then transferred into ECs. [score:1]
HEK-293T cells were transfected with these reporter plasmids (WT, MUT7, and MUT12) together with the miR-27a mimics or NC using Lipofectamine [TM] 2000 (Invitrogen). [score:1]
Saha et al. demonstrated that miR-27a cargo in monocyte-derived extracellular vesicles from the plasma of alcoholic hepatitis patients can program naive monocytes to polarize into M2 macrophages 37. [score:1]
Figure 3c shows the sequence comparison between miR-27a and the 3′ UTR of GRK6. [score:1]
Decreasing the miR-27a level in vivo attenuated the abnormal EC proliferation. [score:1]
The effect of miR-27a and GRK6 on the proliferation of ECs. [score:1]
The strain -induced VSMC-MPs modulated tube formation in vitro (Supplementary Fig. S5), which suggests that VSMC-MPs from high cyclic stretch may deliver miR-27a and promote EC angiogenesis. [score:1]
miR-27a is an important secreted miR that is involved in many physiological and pathological processes. [score:1]
High cyclic stretch induced the secretion of miR-27a via VSMC-MPs. [score:1]
However, the sustain elevation of miR-27a associated with VSMC-MPs induced by high cyclic stretch may results in excess angiogenesis, which may be detrimental to hypertension 39. [score:1]
How to cite this article: Wang, L. et al. Secreted miR-27a Induced by Cyclic Stretch Modulates the Proliferation of Endothelial Cells in Hypertension via GRK6. [score:1]
The presence of B-miR-27a in the cytoplasm of both VSMCs and ECs demonstrated the transmission of miR-27a from VSMCs to ECs via VSMC-MPs. [score:1]
The sequences of the rno-miR-27a mimics were: 5′-UUC ACA GUG GCU AAG UUC CGC-3′ and 5′-GGA ACU UAG CCA CUG UGA AUU-3′; rno-miR-19a mimics were: 5′-UGU GCA AAU CUA UGC AAA ACU GA-3′ and 5′-AGU UUU GCA UAG AUU UGC ACA UU-3′; rno-miR-19b mimics were: 5′-UGU GCA AAU CCA UGC AAA ACU GA-3′ and 5′-AGU UUU GCA UGG AUU UGC ACA UU-3′; rno-miR-217 mimics were: 5′-UAC UGC AUC AGG AAC UGA CUG-3′ and 5′-AGU CAG UUC CUG AUG CAG UAU U-3′. [score:1]
For luciferase reporter experiments, one 60-bp WT oligo from positions 2601–2660 (including the miR-27a seeding site) of the GRK6 3′ UTR or two mutated (MUT) oligos (MUT12 and MUT7) were obtained by gene synthesis (Supplementary Table S2) and inserted downstream of the luciferase reporter gene (psiCHECK-2, Promega). [score:1]
The findings of Jaiswal et al. showed the transmission of miR-27a from the Lucena cell line to the co-cultured recipient cells (breast and lung cancer mo dels) via Lucena-derived MPs 35. [score:1]
The above reports demonstrate the mechanisms or diagnostic significance of secreted miR-27a. [score:1]
miR-27a/b was also reported to promote angiogenesis 38. [score:1]
The six top images show the successful transfection of B-miR-27a in the VSMCs, and the six bottom images show the transfer of miR-27a from VSMCs to ECs. [score:1]
The present study revealed that high cyclic stretch increased the secretion of miR-27a from VSMCs via VSMC-MPs, and the miRs were subsequently transferred to ECs, where they induced EC proliferation. [score:1]
The effect of miR-27a on GRK6 was then further confirmed. [score:1]
These results indicate a positive effect of miR-27a and a negative effect of GRK6 on EC proliferation. [score:1]
Staining of B-miR-27a in ECs and VSMCs was performed using rhodamine-labeled streptavidin (KPL). [score:1]
These results demonstrate that locally decreasing miR-27a in the arteries of hypertensive rats attenuates the abnormal proliferation of ECs. [score:1]
Schematic drawing of the role of secreted miR-27a in abnormal EC proliferation during hypertension. [score:1]
Biotinylated miR-27a (B-miR-27a) was then transfected into VSMCs for miR-27a tracking at a concentration of 30 nmol/L. [score:1]
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9
[+] score: 71
Biochemical pathways potentially regulated by miRNAs differentially expressed in retina of Aβ -injected rats (Figure 3 and Table 4A) and in serum of AMD patients (Figure 4 and Table 4B) have been identified through the web server DIANA-miRPath v. 3. MiR-27a, miR-146a, and miR-155 (Figure 3 and Table 4A), which were up-regulated in retina of Aβ -injected rats, top scored as associated to TGF-β (p = 1 E-10) and prion diseases (p = 2 E-11) pathways. [score:9]
We found down-regulation of miR-155 in serum of AMD patients and Aβ injected rats; whereas we found up-regulation of miR-155 in the retina of Aβ injected rats, along with miR-27a and miR-146a. [score:7]
With exception of miRNA-155, down-regulated in serum of AMD patients and in serum of Aβ injected rats, six miRNAs (miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-126) showed an up-regulation in serum of AMD patients. [score:7]
Furthermore, regulation of prion diseases pathway by miR-27a, miR-146a, and miR-155, reinforces the hypothesis that AMD can be a protein misfolding disease, such as AD, due to deposition of Aβ oligomers in drusen bodies. [score:6]
Reduced expression of hsa-miR-27a-3p in CSF of patients with Alzheimer disease. [score:5]
In fact, miR-155 and miR-27a can target 42 genes involved in the TGF-β pathway (DIANA-miRPath), while miR-146a can target genes involved in inflammatory pathways (Toll-like receptor, NF-κB, TNF signaling pathways). [score:5]
Intravitreal injection of Aβ induced the up-regulation of three miRNAs in rat retina: miR-27a, miR-146a, and miR-155 (Table 2 and Figure 1). [score:4]
In particular, up-regulation of miR-9, miR-23a, miR-27a, miR-34a, miR-126, and miR-146a was found in serum of AMD patients. [score:4]
Analysis of these 13 miRNAs revealed that 7 miRNAs showed a significant up-regulation in serum of AMD patients in comparison to control group (miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155, and miR-126). [score:4]
Incidentally, we showed that changes in circulating levels of some miRNAs (miR-9, miR-23a, miR-27a, miR-34a, miR-126, miR-146a, miR-155) as found in AMD patients are associated to Alzheimer's disease and modulate genes involved in neurodegenerative and inflammatory pathways. [score:3]
In conclusion, the modified miRNA levels we found in rat retina (miR-27a, miR-146a, miR-155) and serum of AMD patients (miR-9, miR-23a, miR-34a, miR-126, miR-27a, miR-146a, miR-155) suggest that, among others, miR-27a, miR-146a, and miR-155 have an important role in AMD and could represent suitable biomarkers and appealing pharmacological targets. [score:3]
The following groups of miRNAs were analyzed: miR-27a, miR-146a, miR-155 miR-9, miR-23a, miR-27a, miR-34a, miR-126,miR-146a, miR-155 miR-155 GraphPad Prism (version 4.0; GraphPad Software, San Diego, CA, USA) was used for statistical analysis and graphical representation of miRNA differential expression data. [score:3]
The potential link between AMD and AD is also in line with the deregulation of insulin receptor signaling by miR-27a, miR-146a, and miR-155 (Giuffrida et al., 2012; Gontier et al., 2015; Takach et al., 2015; Han et al., 2016; Sajan et al., 2016; Table 4A). [score:2]
Figure 3 Scatter distribution of pathways regulated by miR-27a, miR-146a, and miR-155. [score:2]
Three miRNAs were found to be dysregulated both in AMD patients and in retina of Aβ -injected rats (miR-27a, miR-146a, miR-155). [score:2]
To our knowledge, dysregulation of miR-27a has not been reported by other authors before, neither in experimental animal mo dels nor in in vitro mo dels of AMD. [score:2]
MiR-27a, miR-146a, and miR-155 have been reported to be associated to the inflammatory pathways mTOR, TNFα, HIF signaling, and NF-κB (Romano et al., 2015). [score:1]
Furthermore, involvement of miR-27 in AD was well documented by other authors (Maes et al., 2009; Sala Frigerio et al., 2013). [score:1]
Wang et al. (2012) suggested for the first time the potential role of miR-27a in AMD. [score:1]
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10
[+] score: 32
At the post-transcriptional level, miR-27a targets the 3′-UTR of the PHB1 gene and down-regulates its expression in prostate cancer [116]. [score:8]
b The short peptide, ERAP, and the natural product derived from medical plants, xanthohumol, could disrupt the PHB2/BIG3 interaction directly and lead to the translocation of PHB2 from cytoplasm to nucleus, thereby, induce cell growth arrest in some estrogen -dependent cancers a PHB1 can be down-regulated by miR-26a, miR-27a, and miR-195; the lncRNA named PHBP1 directly binds to and maintain the stabilization of PHB1 mRNA; the acetylation of histone H3 can also increase the expression of PHB1; phosphorylation of PHB1 at different amino acids determines the activation and function of PHB1. [score:8]
Fig. 4 a PHB1 can be down-regulated by miR-26a, miR-27a, and miR-195; the lncRNA named PHBP1 directly binds to and maintain the stabilization of PHB1 mRNA; the acetylation of histone H3 can also increase the expression of PHB1; phosphorylation of PHB1 at different amino acids determines the activation and function of PHB1. [score:7]
Fletcher CE Androgen-regulated processing of the oncomir miR-27a, which targets Prohibitin in prostate cancerHum. [score:4]
Chen W Emerging role of microRNA-27a in human malignant glioma cell survival via targeting of prohibitinMol. [score:3]
Liu T Tang H Lang Y Liu M Li X MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitinCancer Lett. [score:2]
[1 to 20 of 6 sentences]
11
[+] score: 32
For that reason, rather than selecting the common targets to both algorithms, we chose PicTar algorithm to match upregulated miRNAs (miR-21, miR-98, miR-27a, miR-143, let-7d, miR-126, miR-22) with downregulated putative targets in Ortis et al. and vice versa (Table 4). [score:11]
Using quantitative PCR -based high throughput analysis, we have confirmed upregulation of 7 (miR-21, miR-98, miR-27a, miR-143, let-7d, miR-126, and miR-22) and downregulation of 1 (miR-129) miRNAs out of the 26 activated miRNAs identified in our settings. [score:7]
Eight miRNAs from the PCR-confirmed 11 miRNAs, are common to both in vitro and in vivo inflammation conditions; 7 upregulated (miR-21, miR-98, miR-27a, miR-143, let-7d, miR-126 and miR-22) and one (miR-129) downregulated (Table 3). [score:7]
The expression patterns of miR-27a varied with hyperglycemia in the Gyoto-Kakizaki rat [5], and miRNA-143 overexpression inhibited insulin-stimulated AKT activation and resulted in impaired glucose metabolism [93]. [score:7]
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12
[+] score: 23
Other miRNAs from this paper: rno-mir-27b
Figure S3 Differential expression of miR-27b but not miR-27a between ASCs of LEW and PVG negatively regulated CXCL12 expression and the suppression of CD4 [+] T-cell proliferation. [score:8]
The TF -targeting miRNAs and the number of targeted TF genes predicted by TargetScan or miRanda are provided in Table 6. Of the 16 candidate miRNAs that were predicted by the two algorithms, miR-27 was the most significantly correlated miRNA with cell differentiation functions as annotated by the FAME algorithm. [score:7]
Thus, the putative TF -targeting miR-27 that has been associated with adipogenesis and lipid metabolism was the first potential miRNA to be identified as being differentially regulated in ASCs from rat strains with distinct immune reactivity. [score:4]
Our approach efficiently identified miR-27 among the chosen putative miRNA targets for further validation. [score:3]
ASCs were cultured in basal media consisting of DMEM supplemented with 2 mM L-glutamine and 10% FBS until the cells reached 60% confluency; cells were then transfected with the miR-27b antagomir (α-miR-27), the anti-miR negative control (α-miRNC, Ambion) or CXCL12 siRNA using TurboFect [TM] siRNA Transfection Reagent (Fermentas Life Science) according to the manufacturer's protocol. [score:1]
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13
[+] score: 21
As seen in Figure 3, the expression levels of miR-146a, miR-210 and miR-27a were up-regulated, while the expression levels of miR-135b and miR-33 were down-regulated (* p < 0.05). [score:11]
To validate the altered expression of miRNAs as detected by miRNA microarray, miR-146a, miR-210, miR-27a, miR-135b and miR-33 were selected for confirmation by quantitative real-time PCR. [score:3]
The five differentially expressed miRNAs (miR-146a, miR-210, miR-27a, miR-135b and miR-33) in the TLE rat hippocampus as detected by the Rat miRNA microarray were confirmed using qPCR (Data are presented as the mean ± SEM, * p <0.05; n = 6/TLE rats, n = 6/control). [score:3]
Some deregulated miRNAs were identified both in the TLE patients of Kan’s work and in our rat TLE mo del, such as miR-27a, miR-190, miR-203 and miR-301a. [score:2]
Some of the deregulated miRNAs (miR-146a, miR-210, miR-27a, miR-135b and miR-33) were confirmed using qPCR. [score:2]
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14
[+] score: 20
Thus upregulation of miR-27a* expression upon acute ischemia could be a defense mechanism by the cells to control the translation of CDK5 molecules. [score:8]
miR-27a* is a direct target of cyclin -dependent kinase 5 (CDK5), which is predominantly expressed in the central nervous system [23]. [score:6]
Independently, we also observed that progressive upregulation of miR-27a* correlates to neurogenesis in primary cultures of cortical neurons, thus implicating a major role for miR-27a* in neuronal regulation. [score:5]
miR-125b-2* and miR-488 peaked at 6 h from the onset of stroke, to 1.56 ± 0.28 and 1.36 ± 0.24 fold, respectively in ischemic rat brain whereas miR-27a*, -422a and -627 peaked at 24 h from the onset of stroke, to 5.37 ± 0.46, 1.52 ± 0.28 and 8.53 ± 1.23 fold, respectively (Figure 4). [score:1]
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15
[+] score: 19
Other miRNAs from this paper: rno-mir-28, rno-mir-34a, rno-mir-144, rno-mir-153, rno-mir-155
H [2]S reduced miR-34a expression in hepatocytes of the young rats but has no effect in old ratsTo further study the mechanism of H [2]S on Nrf-2 expression in the liver after I/R, we detected the expression of many miRNAs including miR-34a, miR-28, miR-155, miR-27a, miR-144 and miR-153, which may be involved in regulating the expression of this transcription factor [28]. [score:10]
To further study the mechanism of H [2]S on Nrf-2 expression in the liver after I/R, we detected the expression of many miRNAs including miR-34a, miR-28, miR-155, miR-27a, miR-144 and miR-153, which may be involved in regulating the expression of this transcription factor [28]. [score:8]
The levels of miRNAs (miR-34a, miR-28, miR-155, miR-27a, miR-144 and miR-153) were quantified with a TaqMan PCR kit. [score:1]
[1 to 20 of 3 sentences]
16
[+] score: 17
Other miRNAs from this paper: rno-mir-7a-1, rno-mir-7a-2, rno-mir-7b, rno-mir-145, rno-mir-146a
For example, miR-7 inhibits the invasion and metastasis of cancer cells by regulating Egfr expression [24– 26]; miR-145 inhibits cell proliferation of lung adenocarcinoma by targeting Egfr [27], miR-146a suppresses tumor growth and progression by targeting Egfr in prostate cancer [28]; miR-27a regulates non-small lung cancer by targeting Egfr [29]. [score:17]
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17
[+] score: 13
[31] MiR-27a affects the expression of MMP-13 and IGFBP-5. [32] MiR-93 regulates collagen loss by targeting MMP-3, [33] and miR-125b regulates the expression of Adamts-4 in human chondrocytes. [score:9]
Additionally, we examined the effects of other four downregulated miRNAs (miR-23b, miR-92a, miR-27a, and miR-30a; results from microarray). [score:4]
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18
[+] score: 11
Other miRNAs from this paper: rno-mir-196a, rno-mir-206, rno-mir-214
Nonetheless, the expression levels of the osteogenic genes in the inhibitor and EVs co-treatment group were still higher than that in the non-treatment group, suggesting that there are other factors such as miR-27a and 206a in the EVs regulating these processes. [score:6]
All the inhibitors, mimics and the negative controls for miR-196a, miR-27a and miR-206 were purchased from Ruibo (Guangdong, China). [score:3]
The results showed that three osteogenic-related miRNAs, miR-196a, miR-27a and miR-206, were highly enriched in BMSC-derived EVs. [score:1]
Among the most highly enriched miRNAs in the EVs were miR-196a, miR-27a and miR-206, three miRNAs critical for osteogenesis. [score:1]
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19
[+] score: 11
In this sense, by virtue of miRNAs known mechanism of action, reducing gene expression by binding to the 3'UTR of their targeted genes, a number of evidenced miRNA species (Mir-27a, Mir-103, Mir-17-5p and Mir-130a) might be involved in turning off the 'neuron projection morphogenesis' process in the SHVT group. [score:5]
Other deregulated biological processes included ‘blood vessel development’ (Mir-155, Mir-17-5p and Mir-130a) (FDR = 6x10 [-4]), 'lung development' (Mir-17-5p and Mir-27a) (FDR = 4x10 [-4]), and ‘cell motion’ (Mir-103) (FDR = 8x10 [-4]) (S3 Table). [score:3]
A heatmap built from nominally significant miRNAs between SHVT and NA detected by sRNA-seq are shown in S3 Fig. When comparing the direct sequencing of the samples with the bioinformatic prediction, 28 miRNA species overlapped, from which Mir-27a, Mir-103, Mir-17-5p, Mir-130a, and Mir-155 were nominally significant although the abundance of the latter was observed to be opposite to the one deduced by GSEA (Table 2). [score:2]
Interestingly, this process was the only one involving all four miRNA species with a consistent abundance among microarray -based predictions and sRNA-seq experiments (Mir-27a, Mir-103, Mir-17-5p and Mir-130a) (FDR<1x10 [-4]) (S3 Table). [score:1]
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20
[+] score: 10
But we only found up-regulated miRNAs miR-27a and miR-27b that could target HMGCR. [score:6]
Of these 9 miRNAs, 6 miRNAs including miR-98, miR-27b, miR135a, miR-7a, miR-674-5p and miR-27a were significantly up-regulated by RDX. [score:4]
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21
[+] score: 10
Other miRNAs from this paper: rno-mir-208a
First, MYH7 expression may be upregulated by the microRNA, miRNA-27a, via inhibition of TRβ1 expression [19]. [score:10]
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22
[+] score: 9
As shown in this study, miR-27a was up-regulated in the spleens of infected Wistar rats, which indicates a lower level of regulation of adipocyte differentiation in the host [35]. [score:5]
Another differentially expressed miRNA this time in the host spleen had clear functions in regulation of adipocyte differentiation (miR-27a). [score:4]
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23
[+] score: 9
Of the 46 increased miRNA, sICAM-1 was the predicted target of 6 (miR-23b, miR-27a, miR-99a, miR-100, miR-324-5p, miR-363); PAI-1 was the predicted target of 4 (miR-30a, miR-30d, miR-182, miR-384-5p), E selectin the predicted target of 2 (miR-16; miR-195) and the alpha chain of fibrinogen the predicted target of miR-29c [26]. [score:9]
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24
[+] score: 9
For example, miR-106b, miR-21, miR- 22, miR-19b and miR-25 are known to regulate PTEN and miR-27 and miR-139 repress FoxO1 translation through direct binding to the 3′-UTR [31], [32], [33], [34], [35], [36], [37], [38]. [score:5]
Among the up-regulated miRNAs, miR-106b, miR-25 and miR-19b share the same primary transcripts, and miR-24 and miR-27 share primary transcripts. [score:4]
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25
[+] score: 8
In addition, miR-27a affects the expression of matrix metalloproteinase (MMP)-13 and IGFBP-5 [28], and miR-27b inhibits the IL-1β -induced upregulation of MMP-13 in human osteoarthritic chondrocytes [29]. [score:8]
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26
[+] score: 8
In order, the miRNAs potentially contributing to downregulation of gremlin1 expression were identified as miR-27a/b, miR-23a/b, miR-181a/b/c/d and miR-182 (Figure 4A, 4B). [score:6]
The results disclosed no obvious differences in luciferase activities between the cells treated with miR-23a-5p mimic (p > 0.05), miR-27a-5p mimic (p > 0.05) or miR-27a-3p mimic (p > 0.05), and those treated with negative control mimics. [score:1]
Conserved binding sites for miR-23a/b, miR-27a/b and miR-181a/b/c/d were predicted in 3107–3442 nt region (G3-23-1) and for miR-182 in the 3590–3809 nt region (G3-23-3). [score:1]
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27
[+] score: 8
Other miRNAs from this paper: hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-27a, hsa-mir-30a, hsa-mir-32, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-107, hsa-mir-129-1, hsa-mir-30c-2, hsa-mir-139, hsa-mir-181c, hsa-mir-204, hsa-mir-212, hsa-mir-181a-1, hsa-mir-222, hsa-mir-15b, hsa-mir-23b, hsa-mir-132, hsa-mir-138-2, hsa-mir-140, hsa-mir-142, hsa-mir-129-2, hsa-mir-138-1, hsa-mir-146a, hsa-mir-154, hsa-mir-186, rno-mir-324, rno-mir-140, rno-mir-129-2, rno-mir-20a, rno-mir-7a-1, rno-mir-101b, hsa-mir-29c, hsa-mir-296, hsa-mir-30e, hsa-mir-374a, hsa-mir-380, hsa-mir-381, hsa-mir-324, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-15b, rno-mir-17-1, rno-mir-18a, rno-mir-19b-1, rno-mir-19b-2, rno-mir-19a, rno-mir-21, rno-mir-23a, rno-mir-23b, rno-mir-24-1, rno-mir-24-2, rno-mir-29c-1, rno-mir-30e, rno-mir-30a, rno-mir-30c-2, rno-mir-32, rno-mir-92a-1, rno-mir-92a-2, rno-mir-93, rno-mir-107, rno-mir-129-1, rno-mir-132, rno-mir-138-2, rno-mir-138-1, rno-mir-139, rno-mir-142, rno-mir-146a, rno-mir-154, rno-mir-181c, rno-mir-186, rno-mir-204, rno-mir-212, rno-mir-181a-1, rno-mir-222, rno-mir-296, rno-mir-300, hsa-mir-20b, hsa-mir-431, rno-mir-431, hsa-mir-433, rno-mir-433, hsa-mir-410, hsa-mir-494, hsa-mir-181d, hsa-mir-500a, hsa-mir-505, rno-mir-494, rno-mir-381, rno-mir-409a, rno-mir-374, rno-mir-20b, hsa-mir-551b, hsa-mir-598, hsa-mir-652, hsa-mir-655, rno-mir-505, hsa-mir-300, hsa-mir-874, hsa-mir-374b, rno-mir-466b-1, rno-mir-466b-2, rno-mir-466c, rno-mir-874, rno-mir-17-2, rno-mir-181d, rno-mir-380, rno-mir-410, rno-mir-500, rno-mir-598-1, rno-mir-674, rno-mir-652, rno-mir-551b, hsa-mir-3065, rno-mir-344b-2, rno-mir-3564, rno-mir-3065, rno-mir-1188, rno-mir-3584-1, rno-mir-344b-1, hsa-mir-500b, hsa-mir-374c, rno-mir-29c-2, rno-mir-3584-2, rno-mir-598-2, rno-mir-344b-3, rno-mir-466b-3, rno-mir-466b-4
First, a subgroup of miRNAs (miR-15b-5p, miR-17-5p, miR-18a-5p, miR-19a-3p, miR19b-3p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23b-5p, miR-24-3p, miR-27a-3p, miR-92a-3p, miR-93-5p, miR-142-3p, miR-344b-2-3p, miR-431, miR-466b-5p and miR-674-3p) displayed increased expression levels during latency (4 and 8 days after SE), decreased their expression levels at the time of the first spontaneous seizure and returned to control levels in the chronic phase (Fig. 2, Supplementary Fig. S1). [score:5]
All these miRNAs displayed a peak in expression levels 8 days after SE, except for miR-21-5p, miR-27a-3p, miR-142-3p and miR-674-3p that peaked earlier (4 days after SE). [score:3]
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28
[+] score: 5
miRs were selected for qPCR analysis because they met one of the following criteria: (1) they were myomirs (miRs 1, 133b, and 206) or involved in muscle regeneration (miR-486); (2) they targeted genes implicated in muscle atrophy (miR-23a/b, miR-27); (3) they were expressed in muscle at high levels and were altered after SCI but have unclear roles in muscle atrophy (miR-145); (5) they were not altered after SCI (miRs 17 and 126) and thus provide controls for internal consistency when comparing qPCR and Nanostrings data. [score:5]
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29
[+] score: 5
Several miRNAs, including miR-21, miR-27, miR-31, miR-199a, miR-214 and miR-222 were up-regulated in these mouse mo dels in the same directions and to similar extents as observed in this study [11], [18]. [score:5]
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30
[+] score: 4
VEGF is modulated by miR-20b through HIF1α in cardiomycytes whereas FOXO1 is regulated by miR-27a in cancer cells [26], [27]. [score:2]
1 up 3.7 down 12 down 1.1 miR-10a up 6.4 up 5.2 up 3.5 down 116 down 1.6 snoRNA202 up 3.8 up 4.7 up 3.2 down 6 down 3 miR-27b down 1.4 up 1.9 up 3.2 up 1 up 1 miR-29c up 5.4 up 4.5 up 3.1 up 1.5 down 1.5 miR-345-5p up 14.3 up 31.7 up 2.4 down 4.7 up 1.1 rno-miR-24-1 down 25.3 up 1.2 up 2.1 down 1.2 down 1.9 miR-687 up 3.8 up 1.8 up 2 down 1.7 down 11.5 miR-27a up 34 up 12. [score:1]
Similar observation were also found in miR-27a, miR-101, miR-9, miR-667. [score:1]
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31
[+] score: 4
Moreover, decreased miR-155 and increased miR-27a in the disc may be associated with apoptosis [14, 15], whereas up-regulation of miR-10b and miR-21 is linked to NP cell proliferation [16, 17]. [score:4]
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32
[+] score: 4
Recent studies also indicate that a panel of miRNAs (i. e., miR-10, miR-15b, miR-16, miR-20a, miR-20b, miR-27a, miR-126, miR-145, miR-195, miR-205, and miR-210) is involved in the regulation of VEGF expression in ECs and tumor cells [16]– [26]. [score:4]
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33
[+] score: 4
Furthermore, among these miRNAs, many were found to be involved in angiogenesis, including several with a regulatory function in cell proliferation, the expression of growth factors and extracellular proteolysis, such as miR-497, miR-98, miR-181a, miR-145, miR-29b and miR-27a 24– 29. [score:4]
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[+] score: 4
Other miRNAs from this paper: hsa-mir-23a, hsa-mir-27a, rno-mir-23a
Downregulation of miR-23a and miR-27a following experimental traumatic brain injury induces neuronal cell death through activation of proapoptotic Bcl-2 proteins. [score:4]
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35
[+] score: 4
In rat and monkey, miR-27a is enriched in the myocardium and its expression profile is anti-correlated to Cdh11 with a coefficient of −0.67 and −0.76 (Tables S5 and S7). [score:3]
Notably, the cardiac valve-enriched Cdh11 mRNA contains a miR-27a binding site in rat, dog, cynomolgus monkey and human. [score:1]
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[+] score: 4
Ventral combined with dorsal root avulsion resulted in a sustained upregulation of 10 miRNAs, including miR-19b-3p, miR-20b-5p, miR-21-5p, miR-27a-3p, miR-29b-3p, miR-106b-3p, miR-142-3p, miR-322-5p, miR-352, and let-7a-5p (Figure  2E). [score:4]
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37
[+] score: 3
In addition to the cardiac specific miR-208a-3p and miR-499-5p, we found that the expression of let-7i-5p, miR-16-5p, miR-27a-3p, miR-199a-3p and miR-223-3p was significantly higher in the heart compared to the kidney, independent of the presence of ischemic heart failure (S4 Fig and S5 Table). [score:2]
In AngII mice and controls, miR-26b-5p was significantly correlated to both LVESP (R = 0.66, P-value = 0.037) and dP/dt [max] values (R = 0.66, P-value = 0.038) and in mice with ischemic heart failure and controls we found miR-27a-3p to be borderline significantly correlated to LVEF (R = -0.56, P-value = 0.049). [score:1]
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[+] score: 3
Huang S. et al., 2008 [65] published that the microRNA cluster miR-23a∼miR-27a∼miR-24 decreases TGF-β induced tumor suppressive activities in human liver cancer cells (HCC). [score:3]
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39
[+] score: 3
MiRNA-21 (A), miRNA-199a (B), miRNA-130b (C), miRNA-138-1 (D), miRNA-9 (E), miRNA-27a (F), miRNA-125a (G), and miRNA-320 (H) expression was not validated at 3 days after treatment with BM-MSC. [score:3]
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40
[+] score: 3
Activation of a novel c-Myc-miR27-prohibitin 1 circuitry in cholestatic liver injury inhibits glutathione synthesis in mice. [score:3]
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41
[+] score: 3
Eleven miRNAs, including miR-145-5p, miR-34c-5p, miR-365-3p, miR-214-3p, miR-151, miR-27a, miR-153-5p, miR-365-3p, miR-33-5p, miR-217-5p and miR-129-5p, were differentially and significantly expressed (P < 0.05; Figure 2B). [score:3]
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42
[+] score: 3
Other miRNAs from this paper: rno-mir-21, rno-mir-126a, rno-mir-127, rno-mir-126b
Microarray -based expression profiles in our previous study have identified several miRNAs in EPCs, such as microRNA 21 (miR-21), microRNA 27a (miR-27a), and microRNA 126 (miR-126) [9]. [score:3]
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[+] score: 3
In retrospect, such miRNAs as miR-9, miR-27 (Gene ID: 407018), miR-140 (Gene ID: 406932), and miR-146 have been indicated to be abnormally expressed in OA patients. [score:3]
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44
[+] score: 3
Other miRNAs from this paper: rno-mir-27b
The elevated ROS production was reduced by transfection of miR-27 IN (p<0.01) and the effect was blocked by Nrf2 knockdown (p<0.01) (Figure 8B). [score:2]
The results indicated that miR-27 AM further promoted the decrease in miR-27b level caused by ICH (p<0.01), as shown in Figure 4A. [score:1]
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45
[+] score: 3
Other miRNAs from this paper: rno-mir-203a, rno-mir-203b
25miR-10b-1.30.20-1.100.30miR-1451.10.400.940.35miR-3501.40.351.100.50 miR-27a -1.3 0.44 -1.20 0.49 miR-203 expression level increases significantly (p<. [score:3]
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46
[+] score: 3
Salvi A. Abeni E. Portolani N. Barlati S. de Petro G. Human hepatocellular carcinoma cell-specific miRNAs reveal the differential expression of miR-24 and miR-27a in cirrhotic/non-cirrhotic HCC Int. [score:3]
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47
[+] score: 3
We found that miRNAs with higher expression in WBCs includes different miRNA families: mir-15, mir-17, mir-181, mir-23, mir-27 and mir-29 families. [score:3]
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48
[+] score: 2
In adults, ethanol causes systemic release of miR-155 and miR-27a to regulate TLR4 signaling and monocyte activation state, respectively [60, 61]. [score:2]
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49
[+] score: 2
After the FO diet, miR-380–5p, miR-27a-3p, and miR-500–3p expressions decreased compared with the SO diet. [score:2]
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50
[+] score: 2
Several miRNAs, such as miR-122, miR-451, miR-200b and miR-27, have been found to be deregulated in different diet -induced NAFLD rat mo dels [15]. [score:2]
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51
[+] score: 2
Guttilla et al. have shown that FOXO1 can be coordinately regulated by miR-27a, miR-96, and miR-182 38. [score:2]
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52
[+] score: 1
Other miRNAs from this paper: rno-mir-124-3, rno-mir-124-1, rno-mir-124-2
[28] Furthermore, it has been recently reported that various microRNAs including miR-27a, -29b, -125a, -146a -155, and -222 are implicated in polarized phenotypes of macrophages. [score:1]
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53
[+] score: 1
The authors also demonstrated that resilient rats differed from vulnerable rats in the set of multiple blood-circulating miRNAs, namely, reduction in miR-139-5p, miR-28-3p, miR-326-3p, and miR-99b-5p in resilient animals and reduction in miR-24-2-5p, miR-27a-3p, miR-30e-5p, miR-3590-3p, miR-362-3p and miR-532-5p levels in vulnerable animals. [score:1]
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We began by measuring the levels of several miRNAs reportedly associated with cardiovascular diseases, including mir-129, mir-106, mir-26a, mir-20, mir-197, mir-17, mir-27 and mir-30d, 24, 25, 26, 27, 28, 29 in cardiomyocytes under both normal and high-glucose conditions. [score:1]
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55
[+] score: 1
Other miRNAs from this paper: rno-mir-155
Banerjee N. Talcott S. Safe S. Mertens-Talcott S. U. Cytotoxicity of pomegranate polyphenolics in breast cancer cells in vitro and vivo: Potential role of miRNA-27a and miRNA-155 in cell survival and inflammationBreast Cancer Res. [score:1]
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56
[+] 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-21, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-33a, hsa-mir-98, hsa-mir-29b-1, hsa-mir-29b-2, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-126a, mmu-mir-133a-1, mmu-mir-135a-1, mmu-mir-141, mmu-mir-194-1, mmu-mir-200b, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-203a, hsa-mir-211, hsa-mir-218-1, hsa-mir-218-2, hsa-mir-200b, mmu-mir-300, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-141, hsa-mir-194-1, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, 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-21a, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-27a, mmu-mir-98, mmu-mir-326, rno-mir-326, rno-let-7d, rno-mir-343, rno-mir-135b, mmu-mir-135b, hsa-mir-200c, mmu-mir-200c, mmu-mir-218-1, mmu-mir-218-2, mmu-mir-33, mmu-mir-211, mmu-mir-29b-2, mmu-mir-135a-2, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-30e, hsa-mir-326, hsa-mir-135b, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, 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-21, rno-mir-26b, rno-mir-27b, rno-mir-29b-2, rno-mir-29a, rno-mir-29b-1, rno-mir-29c-1, rno-mir-30c-1, rno-mir-30e, rno-mir-30b, rno-mir-30d, rno-mir-30a, rno-mir-30c-2, rno-mir-33, rno-mir-98, rno-mir-126a, rno-mir-133a, rno-mir-135a, rno-mir-141, rno-mir-194-1, rno-mir-194-2, rno-mir-200c, rno-mir-200a, rno-mir-200b, rno-mir-203a, rno-mir-211, rno-mir-218a-2, rno-mir-218a-1, rno-mir-300, hsa-mir-429, mmu-mir-429, rno-mir-429, hsa-mir-485, hsa-mir-511, hsa-mir-532, mmu-mir-532, rno-mir-133b, mmu-mir-485, rno-mir-485, hsa-mir-33b, mmu-mir-702, mmu-mir-343, mmu-mir-466b-1, mmu-mir-466b-2, mmu-mir-466b-3, hsa-mir-300, mmu-mir-511, rno-mir-466b-1, rno-mir-466b-2, rno-mir-532, rno-mir-511, mmu-mir-466b-4, mmu-mir-466b-5, mmu-mir-466b-6, mmu-mir-466b-7, mmu-mir-466b-8, hsa-mir-3120, rno-mir-203b, rno-mir-3557, rno-mir-218b, rno-mir-3569, rno-mir-133c, rno-mir-702, rno-mir-3120, hsa-mir-203b, mmu-mir-344i, rno-mir-344i, rno-mir-6316, mmu-mir-133c, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-mir-30f, mmu-let-7k, mmu-mir-3569, rno-let-7g, rno-mir-29c-2, rno-mir-29b-3, rno-mir-466b-3, rno-mir-466b-4, mmu-mir-203b
Type of site Context+ Context Structure Energy Is experimental validated rno-miR-344i MIMAT0025049 2 8mer −0.42 −0.334 297 −32.2 TURE rno-miR-6316 MIMAT0025053 2 8mer, 7mer-m8 −0.41 −0.611 308 −29.59 TRUE rno-miR-21-3p MIMAT0004711 2 8mer, 7mer-m8 −0.408 −0.581 289 −25.18 TRUE rno-miR-3120 MIMAT0017900 2 7mer-m8 −0.402 −0.536 289 −24.4 TRUE rno-miR-194-5p MIMAT0000869 3 7mer-m8 offset 6mer −0.381 −0.593 442 −41.91 TRUE rno-miR-126a-3p MIMAT0000832 1 8mer −0.358 −0.248 148 −18.86 TRUE rno-miR-27a-3p MIMAT0000799 3 7mer-m8 −0.357 −0.708 447 −41.04 TRUE rno-miR-26b-5p MIMAT0000797 3 7mer-m8 offset 6mer −0.348 −0.581 444 −30.64 TRUE rno-miR-3557-3p MIMAT0017820 4 8mer 7mer-m8 imperfect −0.346 −0.503 582 −81.21 TRUE rno-miR-27b-3p MIMAT0000798 4 7mer-m8 offset 6mer −0.334 −0.705 588 −55.75 TRUE rno-miR-3569 MIMAT0017849 2 8mer offset 6mer −0.333 −0. [score:1]
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