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71 publications mentioning rno-mir-122

Open access articles that are associated with the species Rattus norvegicus and mention the gene name mir-122. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 398
Other miRNAs from this paper: mmu-mir-122
Taken together, these results suggest that IL-6 and TNF-α decrease miR-122 expression directly by downregulating its transcription factors C/EBPα and HNF3β and indirectly by upregulating c-myc, which blocks the association of C/EBPα with the miR-122 promoter. [score:11]
healthy liver samples from an array dataset [19] revealed that miR-122 target expression increased in chronic hepatitis; on the contrary, the expression of targets of miR-33a, another highly expressed liver mRNA, did not change. [score:11]
Two major inflammatory cytokines in CHB, IL-6 and TNF-α, suppressed miR-122 expression both by downregulating the miR-122 transcription factors C/EBPα and HNF3β and by inducing c-myc -mediated C/EBPα inhibition. [score:10]
IL-6 and TNF-α suppressed miR-122 expression by inhibiting C/EBPα expression and transcriptional activity (Figure 2 and 3), and decreased miR-122 may result in elevated Ccl2 (Figure 1H). [score:9]
Our previous studies show that miR-122 is downregulated in chronic hepatitis B (CHB) and HCC, and upregulation of its target PBF promotes HCC growth and invasion [10, 18]. [score:9]
In turn, miR-122 downregulation promotes further inflammation both directly by increasing inflammatory cytokine expression and indirectly by recruiting inflammatory cells in the liver. [score:8]
Inflammatory cytokine -induced C/EBPα downregulation and c-myc -mediated C/EBPα inhibition suppresses miR-122. [score:8]
Decreased miR-122 expression and increased expression of miR-122 target genes are observed in HCC tumors compared to nontumor tissues, and loss of miR-122 expression is associated with hepatocarcinogenesis, metastasis, poor prognosis, and reduced response to chemotherapy [3, 4]. [score:8]
Our findings demonstrate that inflammatory IL-6 and TNF-α suppress miR-122 by both directly downregulating C/EBPα and indirectly reducing its transcriptional activity, as shown in Figure 6F. [score:8]
As in previous studies, IL-6 and TNF-α increased c-myc expression (Figure 3A), and overexpression and knockdown studies both showed that c-myc suppressed miR-122 expression as measured by real-time PCR (Figure 3B) and northern blotting (Figure 3C). [score:8]
Downregulation of miR-122 results in ADAM17 upregulation, which leads to increased TNF-α production [38]. [score:7]
Given that IL-6 and TNF-α upregulate c-myc expression [25, 26] and that c-myc and miR-122 reciprocally regulate each other in HCC [27], we further investigated whether IL-6 and TNF-α also affect miR-122 expression via c-myc. [score:7]
Moreover, IL-6- and TNF-α -induced decreases in miR-122 expression were largely abolished by simultaneous transfection with C/EBPα siRNA (Figure 2D), indicating that IL-6 and TNF-α suppress miR-122 expression mainly by decreasing the levels of its transcription factor C/EBPα. [score:7]
As shown in Figure 1H, miR-122 mimic -transfected HepG2 cells displayed decreased Ccl2 expression, whereas the inhibition of endogenous miR-122 in Huh-7 cells increased Ccl2 expression. [score:7]
Given that an miR-122 target, Ccl2, may induce the production of IL-6 and TNF-α by lymphocytes in miR-122 KO mice [6], we further determined whether miR-122 regulates Ccl2 expression in hepatocytes. [score:6]
In conclusion, this study indicates that chronic inflammation reduces miR-122 expression through C/EBPα in hepatocytes during chronic hepatitis, and miR-122 downregulation in turn promotes inflammation. [score:6]
miR-33a and miR-122 targets predicted by TargetScan (TS) and miR-122 targets validated by reporter assay (mirbase) were analyzed. [score:6]
Furthermore, in miR-122 KO mice, upregulation of the miR-122 target Ccl2 results in liver inflammation and hepatic infiltration of IL-6- and TNF-α-producing inflammatory cells [6]. [score:6]
As expected, the restoration of miR-122 in DEN -treated mice blocked upregulation of most of the miR-122 target genes implicated in hepatocarcinogenesis, including cyclin G1, PKM2, ADAM10, and iqgap (Figure 6E). [score:6]
IL-6 and TNF-α suppress miR-122 by downregulating C/EBPα. [score:6]
The mean fold change in expression of miR-122 targets was compared to miR-33a targets or all genes; the number of genes in each group is shown. [score:6]
In rat and mouse DEN -induced HCC mo dels, elevated IL-6 and TNFα expression and reduced miR-122 expression were observed in the liver before HCC development. [score:6]
Together with these studies, our current work suggests that proinflammatory cytokines inhibit the transcription factor C/EBPα by repressing both its autoregulation and its transcriptional activity via c-myc, ultimately leading to decreased miR-122 expression in chronic hepatitis. [score:6]
Liver miR-122 expression is decreased, whereas IL-6 and TNF-α expression are increased, in a DEN -induced rat hepatoma mo del. [score:5]
Expression of miR-122 target oncogenes, namely cyclin G1, ADAM10, PKM2, and iqgap, was also increased in the tumors that developed (Figure 6E). [score:5]
Importantly, restoration of miR-122 strongly inhibits tumorigenesis and reduces tumor incidence in miR-122 KO mice, indicating that miR-122 acts as an HCC tumor suppressor [5, 6]. [score:5]
Additionally, miR-122 suppresses Ccl2 expression in hepatocytes, which actively modulate immune responses and inflammation locally in the liver [40]. [score:5]
Notably, blocking DEN -induced miR-122 downregulation with agomiR-122 treatment significantly attenuated HCC development in mice. [score:5]
Competition with purified His-tagged c-myc protein expressed in Escherichia coli showed that c-myc inhibited C/EBPα binding to the miR-122 promoter in a dose -dependent manner (Figure 3J, left), indicating that c-myc binds to C/EBPα and blocks its association with the miR-122 promoter. [score:5]
We then performed a meta-analysis of published miR-122 target gene expression microarray data from chronic hepatitis patients (Figure 1D). [score:5]
Importantly, decreased miR-122 expression enhanced proinflammatory chemokine Ccl2 expression. [score:5]
IL-6 and TNF-α suppress miR-122 by c-myc -mediated C/EBPα inhibition. [score:5]
H. HepG2 cells were transfected with miR-122 mimic or control mimic (left) and Huh-7 cells were transfected with miR-122 inhibitor or control inhibitor (right). [score:5]
Moreover, similar changes in miR-122 primary transcript (pri-miR-122) levels were observed after IL6 or TNF-α treatment (Figure 1G), indicating that these cytokines downregulate miR-122 at the transcriptional level. [score:4]
Mice were treated with DEN 15 days after birth, and agomir-122 or control agomir [30] was intravenously injected 20 times at a dose of 5 nmol/mouse after 5 months (Figure 6A), when miR-122 was significantly downregulated but microscopic tumors had not yet developed. [score:4]
In this study, we demonstrated that major proinflammatory cytokines reduced miR-122 expression, which contributed to HCC development. [score:4]
Thus, both chronic inflammation and viral replication (e. g., transcripts) may be involved in miR-122 downregulation in the liver by HBV or HCV infection. [score:4]
Next, we explored the mechanism of IL-6- and TNF-α -induced miR-122 downregulation. [score:4]
These results indicate that miR-122 downregulation contributes to inflammation -induced HCC. [score:4]
Furthermore, delivery of miR-122 using agomir suppressed HCC development in the context of chronic hepatitis. [score:4]
As IL-6 and TNF-α are major inflammatory factors in chronic hepatitis, these results suggest that chronic inflammation may contribute to miR-122 downregulation in CHB. [score:4]
Moreover, c-myc inhibited miR-122 promoter activity in luciferase reporter assays (Figure 3D), indicating that c-myc affects miR-122 expression at the transcriptional level. [score:4]
C/EBPα overexpression increased, whereas RNAi -induced C/EBPα knockdown decreased, miR-122 levels (Figure 2C). [score:4]
To assess whether miR-122 downregulation is involved in DEN -induced hepatocarcinogenesis, we utilized a cholesterylated stable miR-122 mimic with two oxygen methylation modifications and sulfur -modified phosphate, agomir-122, to deliver miR-122 to mouse livers. [score:4]
Furthermore, increased c-myc levels reduced C/EBPα -mediated activation of the miR-122 promoter (Figure 3K), and c-myc suppressed the activity of the wild type miR-122 promoter but not a promoter with mutations in the two C/EBPα binding sites (Figure 3L). [score:4]
miR-122 was downregulated in a dose -dependent manner 4 hours after treatment with between 1 and 1,000 U/ml of IL6 or TNF-α (Figure 1F). [score:4]
Inflammatory cytokines suppress miR-122 in CHB. [score:3]
G. Huh-7 cells were treated with 1000 IU/ml IL-6 or TNF-α for 12 h. The expression of pri-miR-122 was analyzed by real-time PCR. [score:3]
A. Analysis of miR-122 expression in liver biopsy specimens from CHB patients, HCC tumors, and healthy controls (HC) by real-time PCR. [score:3]
Expression of IL-6 and TNF-α in the liver increased 3-6 months after DEN treatment (Figure 5B), and miR-122 levels simultaneously decreased (Figure 5C). [score:3]
Restoration of miR-122 levels by agomir-122 delivery suppressed DEN -induced hepatocarcinogenesis. [score:3]
Although chronic inflammation causes metachronous multicentric hepatocarcinogenesis, it is still unclear if inflammation affects miR-122 expression. [score:3]
As chronic inflammation may elevate serum alanine aminotransferase (ALT) levels in CHB, we further examined the correlation between ALT and miR-122 expression in CHB patients. [score:3]
Figure 1 A. Analysis of miR-122 expression in liver biopsy specimens from CHB patients, HCC tumors, and healthy controls (HC) by real-time PCR. [score:3]
E. Real-time analysis of miR-122 levels and levels of the miR-122 target genes in liver tissues. [score:3]
As shown in Figure 3G, c-myc did not influence the expression of miR-122 transcription factors. [score:3]
In contrast to its supportive role in HCV, miR-122 reduces HBV expression and replication [18, 31], suggesting that miR-122 treatment might be most effective for HCC arising in the context of HBV infection. [score:3]
Agomir-122 restores miR-122 levels and suppresses DEN -induced hepatocarcinogenesis. [score:3]
Several studies indicate that HBV X protein suppresses miR-122 transcription via binding to PPARγ, and HBV and HCV RNA/mRNAs with miR-122 binding sites sequester endogenous miR-122, which decreases its levels [10, 33, 34, 35]. [score:3]
E. Huh-7 cells were treated with 1000 IU/ml IL-6, TNF-α, IL-1α, IL-1β, TGF-β, IFN-γ, IFNα, or PBS as a control for 12 h. miR-122 expression was detected by real-time PCR. [score:3]
A panel of cytokines implicated in chronic liver hepatitis, including IL-1α, IL-1β, IL6, TNF-α, TGF-β, IFN-γ, and IFN-α [11, 13], was screened to assess their effects on miR-122 expression. [score:3]
Multiple genes targeted by miR-122 are involved in hepatocarcinogenesis, including the oncogenes cyclin G1, a disintegrin and metalloprotease family 10 (ADAM10), serum response factor (SRF), insulin-like growth factor 1 receptor (Igf1R), Wnt1, RhoA, pituitary tumor-transforming gene 1 (PTTG1) binding factor (PBF), and AKT3, as well as the glycolytic gene pyruvate kinase M2 (PKM2) [2, 3, 7– 10]. [score:3]
However, activity of full-length and truncated miR-122 promoter fragments with no c-myc binding sequences was similarly inhibited in pcDNA3.1-c-myc plasmid -transfected cells (Figure 3F). [score:3]
As shown in Figure 1E, treating Huh-7 cells that constitutively express miR-122 with IL-6 or TNF-α decreased miR-122 levels by 51.2% and 51.7%, respectively (p<0.01 for both). [score:3]
In this mo del, miR-122 acts as an HCC suppressor, and inflammation -induced decreases in miR-122 levels contribute to hepatocarcinogenesis. [score:3]
Major inflammatory cytokines in CHB suppress miR-122. [score:3]
F. Schematic figure showing how IL-6/TNF-α- C/EBPα-miR-122 may mediate inflammation and HCC development in hepatitis. [score:2]
miR-122 is involved in various physiological and pathological processes in the liver, such as liver development, lipid metabolism, stress responses, and viral infections [2]. [score:2]
In this study, we identified an inflammation-C/EBPα-miR-122 regulatory loop in chronic hepatic inflammation. [score:2]
Compared to untreated rats, DEN -treated rats had higher IL-6 and TNF-α expression and lower miR-122 levels in liver tissues after 20 weeks of treatment (Figure 4B). [score:2]
Similar results were observed with a miR-122 promoter containing mutated c-myc binding sites (data not shown), indicating that the negative regulation of miR-122 by c-myc is independent of its binding to the miR-122 promoter. [score:2]
Next, we investigated the mechanisms underlying c-myc -mediated miR-122 downregulation. [score:2]
There is growing evidence that miR-122 is important in the development and metastasis of hepatocellular carcinoma (HCC). [score:2]
Therefore, in this study we investigated the possible mechanisms underlying miR-122 downregulation during liver inflammation. [score:2]
In addition, miR-122 knockout (KO) mice develop hepatitis, fibrosis, and HCC. [score:2]
Our results also suggest that the restoration of miR-122 levels may be a novel therapeutic approach for preventing HCC development in patients with chronic hepatitis. [score:2]
miR-122 levels were much higher in patients with low ALT levels (normal range: 10-40 U/L) than in patients with higher ALT levels (0.84±0.072 vs. [score:1]
Furthermore, elevated IL-6 and TNF-α and decreased C/EBPα and miR-122 levels were also observed in DEN -induced rat and mouse HCC mo dels. [score:1]
Decreased miR-122 is correlated with IL-6 and TNFα induction in diethylnitrosamine (DEN) -induced inflammation and HCC in mice and rats. [score:1]
A. Schematic diagram of agomir-miR-122 treatment in mice. [score:1]
miR-122 levels were assessed 48 h after transfection by real-time PCR. [score:1]
As shown in Figure 6B, treatment with agomir-122 largely restored miR-122 levels in DEN -treated mice; their miR-122 levels were similar to those in untreated control mice. [score:1]
To verify three predicted c-myc binding sites on the miR-122 promoter, pGl-122 (−5.3/−3.8k) containing 2 c-myc binding sites and pGl-122 (−5.3/−4.6k) containing no binding sites were constructed using KpnI & XhoI double digestion. [score:1]
Importantly, miR-122 restoration effectively reduced inflammation -mediated HCC incidence, suggesting that miR-122 may be a useful therapy in chronic hepatitis. [score:1]
Decreased miR-122 is correlated with IL-6 and TNF-α induction in a DEN -induced mouse HCC mo del. [score:1]
Two truncated miR-122 promoter fragments, pGL-122 (−5.3/−3.8k) and pGL-122 (−5.3/−4.6k), were constructed. [score:1]
B. Real-time PCR detection of IL-6 and TNF-α mRNA levels (left) and miR-122 levels (right) in liver tissues. [score:1]
miR-122 levels were assessed 48 h after transfection by real-time PCR (B) and northern blotting (C). [score:1]
Several lines of evidence show that decreased miR-122 may be associated with inflammation. [score:1]
This C/EBPα-miR-122 inflammatory feedback circuit may contribute to maintaining an inflammatory microenvironment and promote inflammation -driven HCC. [score:1]
B. and C. Curves showing changes in TNF-α mRNA (left), IL-6 mRNA (right) (B), and miR-122 (C) levels over time in mouse liver tissues after DEN injection. [score:1]
D. Huh-7 cells were cotransfected with pc3.1-c-myc or pcDNA3.1 as a control or with c-myc siRNA or control siRNA, as well as with pGL-122 with a luciferase reporter under the miR-122 promoter, and pRL-TK. [score:1]
3′-biotin-labeled complementary oligonucelotide pairs containing the C/EBPα binding sequences from the miR-122 promoter were chemically synthesized and annealed. [score:1]
This positive miR-122 feedback loop may initiate a well-described pathogenic sequence of persistent inflammation that would predispose patients to HCC [39]. [score:1]
B. Real-time PCR analysis of miR-122 levels in CHB patients with ALT below and above 40 U/L. [score:1]
Three predicted c-myc binding sites were found in the miR-122 promoter region (-5565nt to -4186 nt) using TESS analysis (http://www. [score:1]
Ten weeks after the last agomir-miR-122 or control agomir injection, all mice were sacrificed and the livers were excised. [score:1]
E. The miR-122 promoter pGL-122 contained three predicted c-myc binding sites (−5.7/−3.8k). [score:1]
Despite the key role of miR-122 in HCC pathogenesis, very little is known regarding its functional relevance in inflammation -mediated HCC. [score:1]
The specificity of C/EBPα binding to the miR-122 promoter was confirmed by depleting C/EBPα in Huh-7 extracts with a C/EBPα antibody (Figure 3J right). [score:1]
The construct pGL-122 (−5.7/−3.8k), containing a luciferase reporter gene under the control of the miR-122 promoter, and pCDNA3.1-C/EBPα was kindly provided by Shi-Mei Zhuang (Sun Yat-Sen University, China). [score:1]
Five and a half months after DEN injection, mice were randomly divided into two groups (5/group) and were intravenously injected with 5 nmol agomir-miR-122 or agomir control. [score:1]
Real-time PCR analysis for miR-122 was performed using a TaqMan miRNA kit (Applied Biosystems, Foster City, CA, USA). [score:1]
Two groups of mice were intravenously injected with 5 nmol cholesterol-conjugated miR-122 (agomir-miR-122) in 0.1 ml saline buffer. [score:1]
Notably, miR-122 levels negatively correlated with ALT levels in CHB patients (p<0.05) (Figure 1C). [score:1]
We purchased cholesterol-conjugated miR-122 mimic and negative control from Ribobio (Guangzhou, China) for RNA delivery in vivo. [score:1]
Together, these results suggest a positive feedback loop between pro-inflammatory cytokines and miR-122 in chronic hepatitis. [score:1]
D. Correlations between miR-122 and TNF-α or IL-6 mRNA levels in all mouse livers by Spearman analysis. [score:1]
Dramatic decreases in miR-122 levels are observed in patients with chronic HBV or HCV infections [18, 32]. [score:1]
As the most abundant liver-specific miRNA, miR-122 accounts for about 70% of the total miRNA population in the adult liver. [score:1]
The liver-enriched transcription factors HNF1α, HNF4α, HNF3β, and C/EBPα were examined first as these cytokines may influence miR-122 transcription [23, 24]. [score:1]
B. Curve showing changes in miR-122 levels over time in mouse liver tissues determined by real-time PCR. [score:1]
C. Correlation analysis of miR-122 levels and serum ALT levels in CHB patients. [score:1]
miR-122 levels in HC were arbitrarily set to 1.0. [score:1]
Spearman analysis revealed a negative correlation between miR-122 levels and IL-6 (r=−0.67, p<0.05) and TNF-α (r=−0.78, p<0.01) levels (Figure 5D). [score:1]
EMSA experiments were then performed using C/EBPα -transfected Huh-7 cell extracts and a biotin-labeled oligonucleotide probe containing the C/EBPα -binding sequence from the miR-122 promoter. [score:1]
Figure 6Five and a half months after DEN injection, mice were randomly divided into two groups (5/group) and were intravenously injected with 5 nmol agomir-miR-122 or agomir control. [score:1]
Liver specimens from 19 CHB and 22 HBV-infected HCC patients were collected for miR-122 analysis. [score:1]
F. miR-122 levels were analyzed after treatment with the indicated amounts of IL-6 (left) or TNF-α (right). [score:1]
To determine whether miR-122 expression is affected by chronic hepatitis, we measured miR-122 levels in liver tissues by real-time PCR. [score:1]
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2
[+] score: 202
INH also decreased the expression of miR-122, which corresponded to the increase of two gene targets: Cyclin G1 and CAT-1. Finally, the aberrant downregulation of miR-125b and miR-106b upregulated the STAT3 expression to stimulate the secretion of inflammatory factors during INH -induced liver injury. [score:13]
Generally, the low expression level of miR-122 and high expression of Cyclin G1 and CAT-1 at both mRNA and protein levels during INH -induced liver injury suggested that miR-122 could upregulate translation. [score:10]
Our results suggested that DNA methylation probably regulates the expression of miRNA genes (miR-122, miR-125b, and miR-106b), affecting the expression of their gene targets (Cyclin G1, CAT-1, and STAT3) and participating in the process of INH -induced liver injury. [score:8]
In the present study, the expression levels of hepatic miR-122, miR-106b and miR-125b were downregulated and correlated with liver pathology scores and serum AST and ALT activities, suggesting that the dynamic change in the expression levels of miR-122, miR-106b and miR-125b were related to INH -induced liver injury. [score:8]
Our results suggested that DNA methylation likely regulated the expression of miRNA genes (miR-122, miR-125b and miR-106b), thereby affecting the expression of their target genes (Cyclin G1, CAT-1 and STAT3) and participating in the process of INH -induced liver injury. [score:8]
Two miR-122 gene targets, cell cycle protein G1 (Cyclin G1) and cationic amino acid transporter-1 (CAT-1), also increased at the mRNA and protein levels, which suggests that lower levels of miR-122 contribute to the upregulation of Cyclin G1 and CAT-1 and might play a role in INH -induced liver injury. [score:6]
Finally, we detected the expression levels of their target genes cell cycle protein G1 (Cyclin G1), cationic amino acid transporter-1 (CAT-1) and signal transducer and activator of transcription 3 (STAT3)) and explored the possible regulation mechanisms of miR-122, miR-125b and miR-106b during INH -induced liver injury. [score:6]
These results suggested that methylation was responsible for the downregulation of miR-122, miR-106b and miR-125b expression during INH -induced liver injury. [score:6]
The higher protein levels might suggest that miRNA-122 could upregulate translation. [score:6]
Methylated levels of miR-122, miR-106b and miR-125b were upregulated in INH -induced liver injury and correlated with their expression levels. [score:6]
The amount of methylated miR-122, miR-125b and miR-106b in the liver increased after INH administration and correlated with their expression levels, suggesting the role of methylation in regulating miRNA gene expression. [score:6]
Hepatic miR-122, miR-125b and miR-106b expression levels dramatically decreased after INH administration for 3, 7 and 7 days (* p < 0.05 versus control group)The analysis of Pearson correlation coefficients demonstrated that the expression levels of miR-122, miR-125b and miR-106b were negatively correlated with liver scores (r = − 0.591, − 0.654 and − 0.701, p < 0.001, see Additional file 5: Figure S3) and serum ALT and AST activities (ALT, r = − 0.672, − 0.771 and − 0.695, p < 0.001, see Additional file 5: Figure S1; AST, r = − 0.462, − 0.584 and − 0.606, p < 0.001, see Additional file 5: Figure S2). [score:5]
There was evidence of high miR-122 expression levels in plasma after acetaminophen (APAP) treatment, but their expression levels decreased in the liver [13]. [score:5]
Hepatic miR-122, miR-125b and miR-106b expression levels dramatically decreased after INH administration for 3, 7 and 7 days (* p < 0.05 versus control group) The analysis of Pearson correlation coefficients demonstrated that the expression levels of miR-122, miR-125b and miR-106b were negatively correlated with liver scores (r = − 0.591, − 0.654 and − 0.701, p < 0.001, see Additional file 5: Figure S3) and serum ALT and AST activities (ALT, r = − 0.672, − 0.771 and − 0.695, p < 0.001, see Additional file 5: Figure S1; AST, r = − 0.462, − 0.584 and − 0.606, p < 0.001, see Additional file 5: Figure S2). [score:5]
Furthermore, the expression level of miR-122 has a causal role in higher levels of Cyclin G1 and CAT-1 mRNA and protein expression. [score:5]
We analysed the methylation and expression levels of miR-122, miR-125b and miR-106b and their potential gene targets in livers. [score:5]
We have revealed that INH decreased the expression of miR-122, which corresponded with the increase of Cyclin G1 and CAT-1. However, we revealed a situation in which the expression level of miR-122 did not continuously decrease after INH administration. [score:5]
Thus, the correlation between the expression levels and methylation of CpG islands of the miR-122, miR-125b and miR-106b genes have been revealed, indicating the possibility of epigenetic regulation of these genes during INH -induced liver injury. [score:4]
Therefore, the reduction of miR-122 levels may regulate the target genes, Cyclin G1 and CAT-1, to activate cell proliferation and to repair the damaged liver tissue caused by INH. [score:4]
Thus, we hypothesise that methylation is responsible for the downregulation of miR-122, miR-125b and miR-106b in INH -induced liver injury. [score:4]
We search for putative miR-122 target genes that may participate in the regulation of liver injury. [score:4]
Our results indicated that the expression level of miR-122 decreased at 3 days after INH administration and declined to a minimum at 14 days, before rising rapidly (Fig.   5). [score:3]
Therefore, we first analysed the expression levels of hepatic miR-122, miR-125b and miR-106b after INH administration and explored their correlation with INH -induced liver injury. [score:3]
The miR-122 expression was significantly lower after 3 days, while both miR-125b and miR-106b significantly decreased after 7 days. [score:3]
Moreover, expression levels of miR-122, miR-125b and miR-106b reached a nadir after 14-, 21-, and 21-day administration. [score:3]
CpG island hypermethylation of miR-122, miR-125b and miR-106b genes correlate with their expression levels. [score:3]
miR-122, miR-106b and miR-125b expression levels are correlated with liver pathology scores and AST and ALT levels, supporting the correlation of these three miRNAs with INH -induced liver injury. [score:3]
miR-122 was one of the most abundant miRNAs in the liver, accounting for up to 72% of all hepatic miRNAs [12], while the expressions of miR-106b and miR-125b not only occur in the liver, but also in many other tissues, including the uterus, ovaries and lungs. [score:3]
Methylated levels of miR-122, miR-125b and miR-106b in INH-administered rat liver tissues were significantly higher than those in the control rats (* p < 0.05 versus control group)We also analysed the correlation between methylation levels and the gene expression of miR-122, miR-125b and miR-106b. [score:3]
CAT-1 and Cyclin G1 genes are miR-122 targets. [score:3]
Fig. 5Expression levels of miR-122, miR-125b and miR-106b in the liver tissue of different groups. [score:3]
Methylated levels of miR-122, miR-125b and miR-106b in INH-administered rat liver tissues were significantly higher than those in the control rats (* p < 0.05 versus control group) We also analysed the correlation between methylation levels and the gene expression of miR-122, miR-125b and miR-106b. [score:3]
We further analysed whether the expression levels of miR-122, miR-106b and miR-125b are correlated with the ongoing liver damage according to liver histopathology and serum ALT and AST activities. [score:3]
Moreover, we clearly found that the expression of miR-122, miR-125b and miR-106b were significantly lower at different times. [score:3]
Relative expression levels of miR-122, miR-125b and miR-106b genes in the liver decreased after INH administration and correlated with the scores of liver pathology and serum AST and ALT activities, suggesting that miR-122, miR-125b and miR-106b are associated with INH -induced liver injury. [score:3]
The results showed the negative correlation between methylation and expression levels of miR-122, miR-125b and miR-106b (miRNA-122, r = − 0.587, p < 0.001; miRNA-125b, r = − 0.536, p < 0.001; miRNA-106b, r = − 0.568, p < 0.001, see Additional file 5: Figure S4). [score:3]
The biological target genes of miR-122 should be taken into consideration. [score:3]
Previous studies identified cell cycle protein G1 (Cyclin G1) and the cationic amino acid transporter-1 (CAT-1) were targets of miR-122 [22, 23]. [score:3]
Expression levels of the selected miRNAs (U6, miR-122, miR-125b and miR-106b) and selected mRNAs (β-actin, Cyclin G1, CAT-1, mitogen-activated protein kinase 14 MAPK14, STAT3, RAR-related orphan receptor gamma (RORγt), IL-17, IL-6, TNF-α, CXCL1 and MIP-2) were quantified using real-time RT-PCR analysis. [score:3]
To our knowledge, this study shows for the first time that hepatic miR-122, miR-125b and miR-106b expression levels gradually decreased during a mo del of INH -induced liver injury. [score:3]
For the first time, we have detected the frequent methylation of miR-122, miR-125b and miR-106b. [score:1]
These results suggested that miR-122, miR-125b and miR-106b participated during the early phases of INH -induced liver injury. [score:1]
Instead, miR-122 levels initially declined before rising. [score:1]
The CpG island methylation of miR-122, miR-125b and miR-106b was analysed using SYBR Green -based quantitative methylation-specific PCR (qMSP). [score:1]
In addition, hepatic miR-122, miR-125b and miR-106b methylation levels significantly increased at 7 days after INH administration. [score:1]
edu/) was used to obtain a 2000 bp promoter sequence in the upstream of miR-122, miR-125b and miR-106b genes. [score:1]
This phenomenon raised the question of what the role miR-122 played during INH -induced liver injury. [score:1]
Agarose gel electrophoresis of the PCR products of gene promoter methylation of (b), miR-122, (e) miR-125b and (h) miR-106b. [score:1]
demonstrated that the methylation levels of miR-122, miR-125b and miR-106b in rat liver tissues treated with INH were significantly higher than those in the control group (Figs.   6c– i and see Additional file  6, p < 0.05 versus control). [score:1]
MiRNA-122 regulated Cyclin G1 and CAT-1 in INH -induced liver injury. [score:1]
The analysis of the promoter region revealed that miR-122, miR-125b and miR-106b had CpG islands within the 2000 bp upstream of the transcriptional start site (Fig.   6a– e), providing the structural basis of DNA methylation. [score:1]
Changes in miRNA profiles, including lower miR-122, miR-106b and miR-125b levels, have been reported in animal mo del studies on drug -induced liver injury. [score:1]
DNA methylation at particular CG dinucleotides within the miR-122 gene promoter (c), miR-125b gene promoter (f) and miR-106b gene promoter (i) in liver tissues from INH-administered rats was determined by qMSP. [score:1]
In this study, lower hepatic levels of miR-122, miR-125b and miR-106b are associated with INH -induced liver injury. [score:1]
MiR-122 is a highly abundant and liver-specific miRNA that accounts for 72% of the total liver miRNA population [12]. [score:1]
To verify this hypothesis, we used qMSP analysis to detect the methylation level of hepatic miR-122, miR-125b and miR-106b. [score:1]
[1 to 20 of 56 sentences]
3
[+] score: 162
Other miRNAs from this paper: rno-mir-33
Similarly, miR-122 expression was upregulated by 47%, and fas target mRNA levels significantly increased, whereas pparβ/δ was no modified, when rats were fed a CD. [score:8]
Although the deregulation of miR-33 and miR-122 has been related to the development of risk factors associated to metabolic diseases, such as obesity and metabolic syndrome, most of the studies on the regulation of lipid metabolism by these two miRNAs have been performed using knockout or antisense mo dels [9]– [12], [17]– [19], [40]. [score:7]
Therefore, the expression of Fas and Pparβ/δ mRNAs, an indirect and a direct target of miR-122, respectively, were modified according to miR-122 levels. [score:7]
Direct miR-122 targets that modulate lipid metabolism are essentially unknown and most of the defined target genes of this miRNA, such as Fas, are indirectly modulated. [score:7]
Specifically, miR-33 and miR-122 are known as major regulators of lipid metabolism in the liver, and their deregulation may contribute to the development of metabolic diseases such as obesity and metabolic syndrome [5], [6]. [score:6]
Therefore, in the liver, there was a direct association between miR-33a and miR-122 levels and the expression of their target genes: abca1 and fas, respectively. [score:6]
The fas mRNA was repressed by GSPE and DHA-OR is consistent with the observation that mRNAs involved in lipogenesis tend to be downregulated when miR-122 is inhibited [10], [54], whereas pparβ/δ mRNA levels were no modified significantly. [score:6]
For instance, mice fed a diet of 58%–60% fat [45], with or without 30% w/v of fructose in the drinking water [46], show a downregulation of miR-122 expression in the liver. [score:6]
The inhibition of miR-122 by antisense oligonucleotides reduces the biosynthesis of cholesterol and FAs and increases the oxidation of FAs in the livers of normal mice, and it reduces both hepatic cholesterol accumulation and the development of a fatty liver during the development of diet -induced obesity in mice [10]. [score:5]
The direct and indirect targets mRNAs levels for miR-122 were also modulated by the three treatments according to their effects on miRNAs levels (Figure 1B and 1C). [score:5]
CD increased miR-33a and miR-122 levels in the liver and modulated the expression of their target genes. [score:5]
For this reason, we have quantified a direct, pparβ/δ, and an indirect, fas, target gene of miR-122. [score:5]
The liver expression of target genes of miR-122 and miR-33a indicate that these rats had increased lipogenesis, decreased fatty acid oxidation and reduced HDL biosynthesis in the liver. [score:5]
Moreover, when GSPE and DHA-OR were administered simultaneously, the reduction in miRNA expression was greater than when they were administered separately, with reduction in miR-122 expression of 68%. [score:5]
miR-122 plays a critical role in liver homeostasis by regulating genes with key roles in the synthesis of triglycerides (TGs) and fatty acids (FAs), such as FA synthase (FAS) and sterol regulatory element -binding protein 1c (SREBP1c), as well as genes that regulate FA β-oxidation [7], [8]. [score:4]
However, recently it has been identified PPARα, β, and γ and the PPARα-coactivator (Smarcd1/Baf60a), as direct targets of miR-122 [49]. [score:4]
Moreover, there are several examples in the literature that demonstrate the capacity of polyphenols to modulate miRNAs [33]; for example, we recently reported the ability of grape seed proanthocyanidins to downregulate liver miR-33a and miR-122 in rats [34]. [score:4]
GSPE and DHA-OR reversed the increase in miR-122 and altered their target genes induced by a CD in rat liver. [score:3]
However, mice that were deficient in LDL receptors and that were fed a diet of 22% fat and 0.32% cholesterol do not show any change in miR-122 expression in the liver [48]. [score:3]
However, DHA-OR was more effective and reduced miR-122 expression in the liver by 59%. [score:3]
Liver miR-122 and their target mRNA levels. [score:3]
Experimental details and symbols as in Figure 1. After 3 weeks of GSPE and/or DHA-OR treatments in rats that were fed a CD, the expression of miR-122 in the liver was normalized (Figure 1A). [score:3]
Previously, we have shown that GSPE represses miR-122 and miR-33a liver expression in rats treated with an acute dose, which also induced postprandial hypolipidemia in normal rats [34]. [score:3]
Therefore, like for miR-33a, it seems that diet and genetic modification influence liver miR-122 expression in different ways. [score:3]
Interestingly, these dietary treatments also counteract the overexpression of miR-122, miR-33a that is induced by the CD. [score:3]
But, despite the fact that both treatments repressed the expression of miR-33a and miR-122 in the liver to a similar degree, only the GSPE treatment was effective in reducing the liver lipid content. [score:3]
Additionally, a reduction in liver miR-122 expression was found in genetically obese ob/ob mice [47]. [score:3]
GSPE reduced miR-122 expression by 53%. [score:3]
0069817.g002 Figure 2Experimental details and symbols as in Figure 1. After 3 weeks of GSPE and/or DHA-OR treatments in rats that were fed a CD, the expression of miR-122 in the liver was normalized (Figure 1A). [score:3]
Thus, further studies of liver miR-122 and miR-33 expression using different types of diets are warranted. [score:3]
miR-122 is the most abundant miRNA in the liver and is expressed as a unique miRNA within a single transcript, hcr [54], whereas both miR-33a and b are intronic miRNAs located within Srebf2 and Srebf1, respectively [53]. [score:3]
Moreover, similar to miR-122, DHA-OR was more effective reducing miR-33a expression in the liver than GSPE. [score:3]
It is well-known that miR-122 is involved in the regulation of several genes in the cholesterol biosynthesis pathway [9] and that it modulates TG metabolism [10]. [score:2]
However, to our knowledge, there is not any study showing the influence of ω-3 PUFAs on lipid regulator miRNAs such as miR-33 and miR-122. [score:2]
Both GSPE and DHA-OR treatments repressed miR-122, miR-33a in the liver, reaching the levels found in rats that were fed a STD. [score:1]
However, as with miR-33a, this increase in hepatic miR-122 in rats that were fed a CD has not been observed using other HFD. [score:1]
Therefore, as both treatments repress these miRNAs in the liver and normalize plasma lipids, it could be suggested that the modulation of miR-122 and miR-33a could be one of the molecular mechanisms used by proanthocyanidins and ω-3 PUFAs to improve the plasmatic atherogenic profile that was induced by a CD. [score:1]
We used two well-known dietary components that improve lipid metabolism, proanthocyanidins and ω-3 PUFAs (GSPE and DHA-OR, respectively) to determine whether the improvement in the atherogenic profile induced by these compounds is associated with a reduction in liver miR-122 and miR-33a, which were previously increased by the CD. [score:1]
Consequently, the increase in miR-122 and miR-33a levels in the liver could explain, to some extent, the dyslipemic effect of a CD. [score:1]
In conclusion, the levels of miR-122 and miR-33a in the liver correlate with a state of lipemia in physiological rat mo dels that were nutritionally induced by a cafeteria diet or a cafeteria diet plus hypolipidemic dietary compounds (i. e., GSPE and/or ω-3 PUFAs). [score:1]
Moreover, gene silencing of miR-122 in mice [9], [10], African green monkeys [11] and chimpanzees [12], using either antagomirs or antisense oligonucleotides, significantly decrease plasma cholesterol and TG levels. [score:1]
Specifically, miR-122 and miR-33 play key roles in lipid metabolism. [score:1]
The repression of rat liver miR-122 and miR-33a, induced by GSPE and DHA-OR, was clearly associated with the improvement in the plasma lipid profile that was induced by these two treatments. [score:1]
The effects of GSPE and DHA-OR on the levels of fas, pparβ/δ, cpt1a and abca1 mRNA in the liver were consistent with the repression of miR-33a and miR-122 that was induced by these treatments. [score:1]
More studies are necessary to elucidate the exact mechanism by which GSPE and DHA-OR repress miR-122 and miR-33a. [score:1]
Once again, there was a powerful effect on fas repression when the two treatments were orally administered simultaneously, a situation that was more effective in repressing miR-122 in the liver than was administrating the compounds separately. [score:1]
For this purpose, we analyzed liver miRNA-33a and miR-122 levels in dyslipidemic cafeteria diet- (CD) fed rats and in rats fed a CD supplemented with proanthocyanidins and/or ω-3 PUFAs, two dietary components that are known to counteract dyslipidemia. [score:1]
Interestingly, in association with the atherogenic lipid profile and fatty liver, the levels of miR-122, miR-33a and srebp2, the host gene of miR-33a, were increased in the livers of rats who were fed a CD. [score:1]
The purpose of this work was to study whether the levels of miR-122 and miR-33a correlate with nutritionally induced lipemia in different rat mo dels; this reflects a more natural physiological state. [score:1]
Thus, it should be stressed that the reduction in hepatic levels of miR-122 and miR-33a was associated with the reduction of lipids in the plasma but not in the liver. [score:1]
In relation to miR-122, our results are supported by evidence that plasma miR-122 is increased in patients with hyperlipidemia [44]. [score:1]
Regardless of the well-defined roles of miR-33 and miR-122 in controlling lipid metabolism in genetic mo dels, the association of these miRNAs with lipemia in pathophysiological conditions is not well understood. [score:1]
[1 to 20 of 52 sentences]
4
[+] score: 147
org, TargetScan and MirTarBase databases Overexpression of putative mir-122 downstream targets: G6PC3, ALDOA, and CSIt is generally accepted that miRNAs exert their function partly by down -regulating the expression of their target genes. [score:12]
The glycometabolism-related genes G6PC3, ALDOA, and CS are putative targets of mir-122To elucidate the downstream mechanism of down-regulated mir-122 expression, we sought to identify mir-122 targets. [score:10]
We further confirmed that mir-122 overexpression suppresses the expression of a luciferase reporter gene containing the putative wild-type but not the mutated mir-122 target sequence from CS 3'UTR in human 293T cells (Figure 5D). [score:9]
They also found that mir-122 is up-regulated in cancer-secreted enclosed vesicles and transfers to normal cells to suppress CS expression and glucose utilization in these cells [22]. [score:8]
To elucidate the downstream mechanism of down-regulated mir-122 expression, we sought to identify mir-122 targets. [score:8]
In addition, Cecchi et al. have demonstrated that HIF-1a (hypoxia -induced factor 1-a), a target of mir-122 expressed in response to hypoxia, was up-regulated in mechanical asphyxia compared with craniocerebral injury, natural death and other causes of death [25, 26]. [score:7]
Importantly, significant correlations with postmortem interval, environmental temperature and age were not observed for mir-122 expression (Figure 3B and Figure 3C), further indicating that mir-122 down-regulation is likely caused by hypoxia shock in mechanical asphyxia death. [score:6]
ALDOA is a glycolytic enzyme that can up-regulated by inhibiting mir-122 in the liver [21, 30]. [score:6]
Overexpression of putative mir-122 downstream targets: G6PC3, ALDOA, and CS. [score:5]
We observed significantly increased G6PC3, ALDOA and CS expression accompanied by reductions in mir-122 expression in mechanical asphyxia specimens, indicating an elevated glucose demand under acute hypoxia conditions. [score:5]
We also reported reversed expression patterns of three predicted mir-122 target genes, G6PC3, ALDOA and CS, which encode metabolic enzymes, in the corresponding human specimens. [score:5]
We also observed reversed expression patterns of the three predicted miR-122 targets, G6PC3, ALDOA and CS, which encode glycometabolic enzymes, in the corresponding specimens. [score:5]
RT-qPCR validation of mir-122 expression in 48 human brain specimens, 36 heart specimens and 18 rats and analyses the relationships between the Ct values of mir-122 expression and postmortem of death, environmental temperature and age. [score:5]
All of these studies demonstrate that mir-122 is down-regulated in hypoxia and can stimulate intracellular glucose by up -regulating G6PC3 and ALDOA regardless of whether it is stimulated by glycolysis or by gluconeogenic factors. [score:5]
Our data suggest that mir-122 and its putative downstream target genes, G6PC3, ALDOA and CS, could serve as biomarkers for mechanical asphyxia and shed light on the pathogenesis of hypoxia in diseases. [score:5]
Further analysis of the RT-qPCR data from the 84 samples found that mir-122 was the most consistently down-regulated miRNA in response to mechanical asphyxia in both types of tissues comparing with the other two death causes. [score:4]
Finally, Miranda et al. have demonstrated that mir-122 is down-regulated intracellularly with the excessive glucose spared from glycolysis going towards storage in breast cancer cells. [score:4]
Our data coordinate with prevails studies indicating that mir-122 regulates the expression of the mRNAs and proteins related to G6PC3 [20], ALDOA [21] and CS [22] in cell cultures. [score:4]
Figure 3 A. mir-122 down-regulation in both brain and cardiac tissues of human and rat from mechanical asphyxia cases compared with specimens from other cases. [score:3]
We ultimately selected mir-122, which was expressed at a significantly low level in the both brain and heart specimens from mechanical asphyxia cases. [score:3]
A. mir-122 down-regulation in both brain and cardiac tissues of human and rat from mechanical asphyxia cases compared with specimens from other cases. [score:3]
D. Dual luciferase reporter analysis of mir-122 and a reporter gene with predicted mir-122 target sequences (wildtype and mutant) in the CS 3'UTR in 293T cells. [score:3]
The glycometabolism-related genes G6PC3, ALDOA, and CS are putative targets of mir-122. [score:3]
Venny analyses of mir-122 targets predicted by the microrna. [score:3]
Venny analyses [16] revealed 25 genes that might be regulated by mir-122 (Figure 4). [score:2]
Our findings indicate that an acute metabolic response to hypoxia occurs in human bodies in cases of mechanical asphyxia and is likely regulated by mir-122. [score:2]
Specifically, mir-122 expression was significantly reduced in the brains and cardiac tissues of mechanical asphyxia cases compared with the specimens from craniocerebral injury and hemorrhagic shock cases. [score:2]
Consistently, mir-122 and protein level analyses from the three cause-of-death mo dels in rats (n = 6) revealed the same trend (Figure 3A and Figure 5C). [score:1]
in the brain specimens and sixteen miRNAs (mir-192, mir-148a, mir-122, etc. ) [score:1]
G6PC3, ALDOA and CS exhibited inverse correlations with mir-122 in specimens from the indicated causes of death and Dual luciferase reporter analysis of CS in 293T cells. [score:1]
Our findings thus indicate that mir-122 reduction might be the response to hypoxia in mechanical asphyxia. [score:1]
Furthermore, G6PC3 is a gluconeogenic enzyme that can be stimulated by mir-122 reduction to contribute to gluconeogenesis [20, 31]. [score:1]
HEK293T cells were infected with c-GFP and mir-122 or mir-122M for 24 h. The cells were then seeded into 24-well plates and co -transfected with 0.5 μg of the respective pGL3-3'UTR construct and 0.05 μg of the pGL-TK vector (Promega). [score:1]
Furthermore, eight miRNAs (mir-31, mir-122, mir-219-2-3p, etc. ) [score:1]
We hypothesized that there are reverse correlations between mir-122 and G6PC3, ALDOA and CS mRNA levels. [score:1]
Kyoungsub et al. found that mir-122 decreased and activated glycolytic metabolism with low ATP synthesis in hepatocellular carcinoma cancer stem cells in a hypoxia microenvironment [27]. [score:1]
RT-qPCR validation of microarray results and the robust reduction of mir-122 in mechanical asphyxia specimens. [score:1]
[1 to 20 of 37 sentences]
5
[+] score: 103
Other miRNAs from this paper: rno-mir-103-2, rno-mir-103-1, rno-mir-107, rno-mir-370, rno-mir-539
Shibata C. Kishikawa T. Otsuka M. Ohno M. Yoshikawa T. Takata A. Yoshida H. Koike K. Inhibition of microRNA122 decreases SREBP1 expression by modulating suppressor of cytokine signaling 3 expressionBiochem. [score:8]
They concluded that srebf1 was an indirect target gene for miRNA-122, but they did not describe the intermediate steps in the signaling cascade that led to the up-regulation of SREBP1. [score:7]
However, it was somewhat surprising because fasn is, according to the miRecords data base, a predicted target gene for miRNA-122-5p, which was reduced by resveratrol, and in fact our transfection experiment showed that the over -expression of miRNA-122-5p induced a significant reduction in FAS protein expression. [score:7]
In addition, Iliopoulos et al. [32] showed that the up-regulation of miRNA-122 induced the increased protein expression of SREBP1. [score:6]
Joven J. Espinel E. Rull A. Aragonès G. Rodríguez-Gallego E. Camps J. Micol V. Herranz-López M. Menéndez J. A. Borrás I. Plant-derived polyphenols regulate expression of mirna paralogs miR-103/107 and miR-122 and prevent diet -induced fatty liver disease in hyperlipidemic miceBiochim. [score:6]
Thus, it could be hypothesized that the increase in FAS protein expression expected as a consequence of miRNA-122-5p down-regulation could be compensated by the decrease expected due to the reduction in SREBP1. [score:6]
In this context, the aim of the present study was to determine whether, as in the case of other polyphenols, this reduction in liver fat was mediated by changes in the expression of miRNA-122-5p, miRNA-103-3p and miRNA-107-3p, which represent more than 75% of total miRNAs in the liver [19, 21, 22, 23, 24, 25], as well as in their target genes. [score:5]
Later on, Shibata et al. [31] reported that silencing miRNA-122 led to decreased SOCS3 expression, which in turn increased STAT3 expression. [score:5]
Taking into account that miRNA are negative regulators of protein translation and that no miRNA-122-5p binding sites are found in the 3′UTR or the coding region of this gene, the authors suggested that miRNA-122 could regulate other genes that, in turn, could affect the transcription of srebf1. [score:5]
In rats treated with resveratrol, we found a significantly decreased expression of miRNA-103-3p, miRNA-107-3p and miRNA-122-5p, which was paralleled by a significant decrease in SREBP1 protein expression. [score:5]
As far as miRNA-122-5p is concerned, taking into account the results of our transfection study, and bearing in mind the results reported by Iliopoulos et al. and Shibata et al. [32, 31], it can be proposed that resveratrol decreases the protein expression of the transcription factor SREBP1 indirectly via miRNA-122-5p. [score:4]
Therefore, SREBP1 was negatively regulated by STAT3 and, consequently, a decrease in miRNA-122 induced a reduction in SREBP1 expression. [score:4]
It has been reported in the literature that different types of polyphenols, such as proanthocyanidins or a mixture extracted from Hibiscus sabdariffa, are able to modify the expression of miRNA-122-5p (a liver specific miRNA and the most abundant one) and the paralogs miRNA-103-3p and miRNA-107-3p in liver [16, 17, 18, 19]. [score:3]
In the case of FAS, protein expression was significantly decreased after transfection of miRNA-122-5p (p < 0.001) (Figure 1B). [score:3]
As shown in Table 1, fasn was a predicted target gene only for miRNA-122-5p. [score:3]
Iliopoulos D. Drosatos K. Hiyama Y. Goldberg I. J. Zannis V. I. MicroRNA-370 controls the expression of microRNA-122 and cpt1alpha and affects lipid metabolismJ. [score:3]
Esau C. Davis S. Murray S. F. Yu X. X. Pandey S. K. Pear M. Watts L. Booten S. L. Graham M. McKay R. MiR-122 regulation of lipid metabolism revealed by in vivo antisense targetingCell Metab. [score:3]
In addition, we reviewed the literature and found that several authors had proposed srebf1 and fasn as target genes for miR-122-5p and miR-107-3p, respectively (Table 1). [score:3]
As far as the lipogenic pathway is concerned, miRecords data base showed that srebf1 was a predicted target gene for miRNA-103-3p and miRNA-107-3p and fasn for miRNA-122-5p. [score:3]
In the present study, we observed that the expression of the three miRNA analysed (miRNA-103-3p, miRNA-107-3p and miRNA-122-5p) was significantly reduced in the liver of rats treated with resveratrol (Table 2). [score:3]
MiRNA-103-3p, miRNA-107-3p and miRNA-122-5p were individually over-expressed in AML12 hepatocytes. [score:3]
The targeted miRNA assay sequences were as follows (source miRBase): rno-miRNA-103-3p: 5′-AGCAGCAUUGUACAGGGCUAUGA-3′ rno-miRNA-107-3p: 5′-AGCAGCAUUGUACAGGGCUAUCA-3′ rno-miRNA-122-5p: 5′-UGGAGUGUGACAAUGGUGUUUG-3′ PCR was performed in an iCycler™–MyiQ™ Real-time PCR Detection System (Applied Biosystems, Foster City, CA, USA). [score:2]
The targeted miRNA assay sequences were as follows (source miRBase): rno-miRNA-103-3p: 5′-AGCAGCAUUGUACAGGGCUAUGA-3′ rno-miRNA-107-3p: 5′-AGCAGCAUUGUACAGGGCUAUCA-3′ rno-miRNA-122-5p: 5′-UGGAGUGUGACAAUGGUGUUUG-3′PCR was performed in an iCycler™–MyiQ™ Real-time PCR Detection System (Applied Biosystems, Foster City, CA, USA). [score:2]
Baselga-Escudero L. Blade C. Ribas-Latre A. Casanova E. Suárez M. Torres J. L. Salvadó M. J. Arola L. Arola-Arnal A. Resveratrol and egcg bind directly and distinctively to miR-33a and miR-122 and modulate divergently their levels in hepatic cellsNucleic Acids Res. [score:2]
Baselga-Escudero L. Pascual-Serrano A. Ribas-Latre A. Casanova E. Salvadó M. J. Arola L. Arola-Arnal A. Bladé C. Long-term supplementation with a low dose of proanthocyanidins normalized liver miR-33a and miR-122 levels in high-fat diet -induced obese ratsNutr. [score:1]
Hepatocytes in a confluence status of approximately 90%, were transfected with Lipofectamine RNAiMAX (Applied Biosystems, Foster City, CA, USA) prepared following the manufacturer’s protocol, with mirVana miRNA mimics of mmu-miRNA-103-3p, mmu-miRNA-107-3p and mmu-miRNA-122-5p (homologous to rno-miRNA-103-3p, rno-miRNA-107-3p and rno-miRNA-122-5p respectively) (Applied Biosystems, Foster City, CA, USA). [score:1]
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6
[+] score: 95
Our metabolic and miR-122 target expression data show that RYGB surgery suppresses gluconeogenesis and stimulates glycolysis, as evidenced by the downregulation of G6pc and upregulation of Aldoa, together with elevated concentrations of glycolysis end products including pyruvate, alanine and lactate in the liver and plasma (Figure 4). [score:13]
Eleven of the altered miRNAs were downregulated (miR-122, miR-93*, miR-872, miR-7*, miR-146a, miR-342-3p, miR-150, miR-139, miR-30a, miR-30e, miR-320), whereas three miRNAs, namely miR-463*, miR-34c* and miR-1188, were upregulated in the RYGB group. [score:7]
By antagonizing miR-122 with LNA (locked-nucleic-acid -modified oligonucleotide)-anti-miR-122 in diet -induced obese mice for 6 weeks, a 30% decrease in total cholesterol levels was achieved without lipid accumulation in the liver and tested miR-122 mRNA targets were similar to our findings except for G6pc, which was upregulated. [score:6]
Glut1, a glucose transporter, was upregulated consistent with the decreased miR-122 expression in the liver and increased levels of hepatic glucose and glycogen were observed, indicating that RYGB promotes glucose transportation and glycogen synthesis. [score:6]
These miR-122 targets in the liver all exhibited >1.5 fold increase in expression ranging from 1.53 to 1.91, except for Glut1 and G6pc. [score:5]
G6pc expression, a validated miR-122 target, is surprisingly reduced >80% in the RYGB group (Figure 3c). [score:5]
Decreased miR-122 levels induced the upregulation of Cs (CS) and Ucp2 (UCP2). [score:4]
G6pc expression was lowered rather than elevated in the hepatic tissue, suggesting perhaps regulatory mechanisms of G6pc other than miR-122 predominate. [score:4]
Bariatric surgery has been shown to markedly alter circulating miRNAs in patients, in particular, downregulation of miR-122 by 94.7%. [score:4]
We then investigated whether miR-122 can directly modulate these mRNA targets by manipulating their expression in the hepatocyte-like B13H cell line (derived from a pancreatic AR42J-B13 cell line transdifferentiated with dexamethasone as primary hepatocytes are phenotypically unstable over the required time frame for the experiment). [score:4]
[14] In fact, miR-122, believed to be a hepatocyte-specific miRNA, was upregulated more than 400-fold during this trans-differentiation process (Supplementary Figure S5), consistent with the hepatic phenotype. [score:4]
Consistent with the aforementioned in vivo findings, the G6pc expression level was not affected by miR-122 in the B13H cell line. [score:3]
The clustered miRNA profiles show clear differentiation of the RYGB and SHAM groups (Figure 1b), wherein the RYGB-altered miRNAs typically exhibited a 1.5- to sixfold change compared with sham-operated rats, with the exception of miR-122, which demonstrated a 56-fold (P=0.0095) downregulation in RYGB-operated animals. [score:3]
We first confirmed miR-122 expression levels in both plasma and liver tissue using Taqman real-time quantitative PCR (Figure 3a). [score:3]
In B13H cells transfected with miR-122 mimic, expression of Cs, Glut1, Fasn, Aldoa, G6pd, Prkab1 and Ucp2 were all reduced (although the last three not significantly) in comparison with controls transfected with scrambled miRNA mimic (Figure 3d). [score:3]
We next examined a group of miR-122 targets, which are involved in key liver metabolic processes, such as the TCA cycle (Cs, citrate synthase), glucose transport (Glut1, glucose transporter protein type 1), pentose phosphate pathway (G6pd, glucose-6-phosphate dehydrogenase), fatty-acid synthesis (Fasn, fatty-acid synthase), energy sensing (Prkab1, adenosine monophosphate (AMP)-activated kinase beta 1), mitochondrial oxidation (Ucp2, uncoupling protein 2), gluconeogenesis (G6pc, glucose-6-phosphatase) and glycolysis (Aldoa, aldolase A). [score:3]
Altered miR-122 expression levels in plasma and liver tissues are responsible for metabolic changes post RYGB surgery. [score:3]
RYGB induced the strongest effects on miR-122, as downregulation of miR-122 was observed in both bariatric patients [13] and our rodent mo del for RYGB, we subsequently focused on investigating miR-122 -mediated metabolic pathways. [score:2]
Plasma miR-122 showed a 99% reduction in levels in RYGB-operated rats compared with SHAM controls, whereas hepatic miR-122 only showed 30% reduction of expression. [score:2]
MiR-122 is a liver-produced miRNA and its less marked reduced expression in the liver compared with plasma suggests a restrained miR-122 release into the blood stream after RYGB surgery. [score:2]
We concluded that miR-122 directly modulated Cs, Glut1, Fasn, Aldoa and to a lesser extent, G6pd, Ucp2 and Prkab1. [score:2]
The single Taqman miRNA assay, mRNA target prediction, protein extraction from the liver and Immunoblot, MiRDIAN miR-122 mimic transfection, and statistical correlation analysis among gut hormones, miRNAome and metabolome are described in SI Materials and Methods. [score:2]
[21] Esau et al. [22] demonstrated that injecting miR-122 antisense oligonucleotide into mice for 5 weeks results in reduced plasma cholesterol levels, increased hepatic fatty-acid oxidation, decreased hepatic fatty-acid and cholesterol synthesis rates; effects that are also seen in primates. [score:1]
In mechanistic studies, manipulation of miRNA-122 levels in a cell mo del induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, tricarboxylic acid cycle, pentose phosphate shunt, fatty-acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery -mediated responses, indicating the powerful homeostatic activity of the miRNAs. [score:1]
We have demonstrated that miR-122 contributed to the control of energy metabolism with increased glucose transportation, glycolysis, TCA cycle, pentose phosphate shunt and fatty-acid oxidation and decreased gluconeogenesis and ketone body generation (Figure 4), suggesting an overall increased energy expenditure status. [score:1]
Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. [score:1]
This is consistent with a previous finding in RYGB patients, where miR-122 decreased significantly (−94.2%, P<0.0001) when comparing baseline and after surgery miR-122 levels. [score:1]
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7
[+] score: 79
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-27a, rno-mir-30a, rno-mir-92a-1, rno-mir-92a-2, rno-mir-96, rno-mir-100, rno-mir-101a, 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
The expression levels of miR-183, miR-96, and miR-182 were most highly up-regulated, whereas miR-122, miR-503, and miR-139-3p exhibited the greatest down-regulation as a result of 17α-E2 treatment. [score:9]
The expression levels of miR-183 (4.61-fold), miR-96 (4.56-fold), and miR-182 (4.29-fold) were most highly up-regulated, whereas miR-122 (9.79-fold), miR-503 (5.88-fold), and miR-139-3p (1.94-fold) showed the greatest down-regulation as a result of 17α-E2 treatment. [score:9]
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]
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]
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]
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]
In contrast, dexamethasone down-regulated the expression of several of the miRNAs by more than 1.5 fold, i. e., miR-122 (8.2-fold), miR-466b (2.31-fold), miR-200b (1.9-fold) miR-877 (1.61-fold), miR-296 (1.61-fold)and precursor of miR-504 (1.53-fold) (Fig. 2D ). [score:6]
miR-296 and miR-122 were down-regulated (>1.5 fold) by both 17α-E2 and DEX. [score:4]
The expression levels of miRNA-122 and miRNA-96, however, were not affected by cAMP stimulation. [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]
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]
The levels of expression of miRNA-212, miRNA-122, miRNA-138, miRNA-214, miRNA-183, miRNA-182, miRNA-132, miRNA-96, miRNA-466b, miRNA-200b, and miRNA-19a are shown. [score:3]
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]
Dexamethasone treatment decreased miRNA-200b, miR-122, miR-19a, miRNA-466b and miRNA27a levels, but increased miRNA-183 levels. [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]
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8
[+] score: 77
Other miRNAs from this paper: hsa-mir-122
Based on the previous evidence linking epigenetics with stroke occurrence, and in order to reinforce the involvement of miR-122 in this pathological condition, we presently tested the hypothesis that a derangement of brain miR-122 expression level could be an early marker of cerebrovascular disease in our animal mo del. [score:5]
In fact, miR-122 was shown to be downregulated both in animal mo dels of ischemic stroke, including the MCAO rat mo del [7, 8], and in peripheral blood cells of patients suffering from ischemic stroke [7, 10, 11]. [score:4]
The same stimuli were applied to cell dishes in the presence of exogenous mimic miR-122 overexpression. [score:3]
The correlation between miR-122 levels and protein expression levels was conducted by using the Pearson correlation test. [score:3]
In the latter mo del, intravenous administration of exogenous miR-122 led to inhibition of proteins involved in inflammation such as intercellular adhesion molecule 1 (ICAM-1) and, most importantly, to reduced brain injury and neurological deficits [9]. [score:3]
In order to assess the brain miR-122 expression level in SHRSP and SHRSR under both JD and RD, tissue total RNA was obtained using TRIzol reagent (Life Technologies, Carlsbad, CA, USA), subjected to DNAse I treatment (Qiagen, Venlo, Netherlands) and subsequently purified using miRNeasy Mini Kit (Qiagen) according to the manufacturer's instructions. [score:3]
Results were expressed as relative levels of miR-122 under the different experimental conditions. [score:3]
In particular, we showed that the overexpression of miR-122 was able to rescue the cell death induced by both excess NaCl and hydrogen peroxide in a line of brain endothelial cells. [score:3]
In particular, the brain miR-122 expression level was significantly increased in the SHRSR, whereas it was significantly decreased in the SHRSP. [score:3]
Correlation Analysis between miR-122 and Protein Expression Levels in the Two Strains. [score:3]
In order to support the in vivo findings and the hypothesis that miR-122 may be involved in cerebrovascular disease pathogenesis, we tested in vitro the ability of miR-122 to maintain cell survival upon two different stress stimuli. [score:3]
In vitro, the overexpression of miR-122 revealed a significant protective effect on survival in cerebral endothelial cells exposed either to excess NaCl or to hydrogen peroxide. [score:3]
At the end of 4 weeks of dietary treatment, miR-122 expression level was significantly increased in the brains of JD- versus RD-fed SHRSR, whereas it was significantly decreased in the brains of JD- versus RD-fed SHRSP (Figure 1(a)), thus reproducing previous findings in other animal mo dels and in humans [7– 11]. [score:3]
The results of the correlation analysis between miR-122 and protein expression levels are shown in Figure 4 (SHRSP strain) and in Figure 5 (SHRSR strain). [score:3]
Brain Expression of MicroRNA-122 in SHRSP and SHRSR. [score:2]
Interestingly, we detected a differential modulation of brain miR-122 expression level after 4 weeks of high-salt dietary regimen, before stroke occurrence, in the SHRSP as compared to the SHRSR strain. [score:2]
Consistently with our current evidence, the miRNA-122 has been involved in the regulation of inflammation and of cell proliferation through the interference with the NF-kB and toll-like receptor signaling pathways [10]. [score:2]
Herein, the involvement of miR-122 on the regulation of several genes and pathways associated with ischemic stroke, including leukocytes activation and thrombus formation, was demonstrated [10]. [score:2]
As a limitation of our current study, we did not test the impact of exogenous miR-122 administration on the stroke phenotype occurrence of JD-fed SHRSP. [score:1]
In fact, substantial changes in markers of oxidative stress, inflammation, endothelial dysfunction, apoptosis, and necrosis could be detected along with the miR-122 decrease in the brains of SHRSP. [score:1]
On the other hand, levels of miR-122 in the SHRSR positively correlated with CD31 and p-eNOS levels, whereas they negatively correlated with the levels of NF-kB, caspase 3, and vWF (Figure 5). [score:1]
Notably, a decrease of miR-122 level was also detected in blood cells of acute ischemic stroke patients [7, 10, 11]. [score:1]
For the latter purpose, a specific miR-122 mimic (miRvana miRNA mimic, Thermo Fisher, Waltham, USA) was incubated in OPTIMEM (Thermo Fisher) reduced serum medium with a nucleic acid transferring agent (lipofectamine RNAiMAX reagent, Invitrogen, Carlsbad USA) in a final volume of 2 ml/well each for 20 min, following the manufacturer's instructions. [score:1]
In the latter strain, the miR-122 decrease was associated with the early signs of cerebrovascular damage. [score:1]
On the other hand, higher levels of miR-122, as those found in the brains of SHRSR, appear to be protective and, in fact, they were able to preserve cell survival from stress stimuli in vitro. [score:1]
The efficiency of miR-122 mimic transfection was validated by RT-PCR. [score:1]
Levels of miR-122 increased in cells transfected with mimic miR-122 (5.32 ± 0.05 fold changes versus nontransfected cells at 24 hrs; 5.84 ± 0.032 fold changes versus nontransfected cells at 72 hrs). [score:1]
Impact of miRNA122 on Cell Viability, Apoptosis, and Necrosis in MECs. [score:1]
Notably, vWF and ICAM-1 were previously reported to be modulated in association with miR-122 changes in animal mo dels of ischemic stroke [9]. [score:1]
Importantly, to further support our hypothesis, we presently provide a clear cut in vitro demonstration of the significant protective effect of exogenous administration of miR-122 on cell survival upon exposure to stress stimuli. [score:1]
Among others, the microRNA-122 (miR-122) level was significantly reduced in the blood of ischemic rats [8] and in both blood and brain tissues of the middle cerebral artery occlusion (MCAO) rat mo del [9]. [score:1]
Our findings support the use of microRNAs, such as miR-122, as useful biomarkers for stroke prevention and diagnosis. [score:1]
The transfection with mimic miR-122 of MECs exposed to either NaCl or H [2]O [2] rescued the cell viability and reduced apoptosis and necrosis in a significant manner. [score:1]
It has been previously associated with miR-122 levels in other experimental mo dels of stroke [9]. [score:1]
For this purpose, the brain miR-122 level was assessed at the end of one month of JD feeding in SHRSP, before the stroke phenotype occurrence. [score:1]
In Vitro Effects of Mimic miRNA-122 on Rat Brain Microvascular Endothelial Cells Viability. [score:1]
Interestingly, based on our findings, miR-122 may be a contributor to stroke resistance in the SHRSR strain. [score:1]
The overall findings of our investigation suggest that miR-122 plays a contributory role in the pathogenesis of cerebrovascular disease, therefore supporting previous evidence [6, 9]. [score:1]
By performing this statistical test, we were able to obtain a significant linear inverse relationship between miR-122 level and levels of Gp91phox, Nf-kB, vWF, ICAM1, CD31, c-Jun, and caspase 3 in the SHRSP (Figure 4). [score:1]
In summary, the different modulation of miR-122 level, associated with the early signs of cerebrovascular damage, was detected in the brains of SHRSP after four weeks of the stroke permissive diet, before the occurrence of cerebrovascular events. [score:1]
At the end of each stress exposure, performed both in the absence or in the presence of exogenous mimic miR-122, we assessed the effect of miR-122 on cell viability, apoptosis, and necrosis by fluorescent-activated cell sorting (FACS) (Accuri C6 flow cytometer, BD Biosciences, San Jose, CA, USA), following previously reported procedures (16). [score:1]
In addition, the exogenous administration of miR-122 to MCAO rats reduced the brain infarct size and the neurological deficits with improvement of stroke outcomes [9]. [score:1]
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9
[+] score: 74
Other miRNAs from this paper: rno-mir-103-2, rno-mir-103-1
The miR-122 inhibitor is a single-stranded oligonucleotide designed to inhibit the endogenous miR-122 function (Applied Biosystems). [score:5]
MicroRNA-122 regulates Cyp7a1 via inhibition of mRNA translation, and may explain the difference between increased mRNA and decreased protein levels of Cyp7a1 in IUGR+HFD female rats (Song et al., 2010). [score:5]
In addition to transcriptional regulation of Cyp7a1 by transcription factor Lxrα, Cyp7a1 is also regulated by microRNA-122 (miR-122), a small RNA that destabilizes Cyp7a1 mRNA thus decreasing Cyp7a1 translation and bile acid synthesis (Song et al., 2010). [score:5]
IUGR+HFD rats were injected with a miR-122 inhibitor to test the ability to normalize the IUGR+HFD phenotype or with a scrambled sequence as a control. [score:3]
These findings suggest that one pathway through which IUGR induces hepatic cholesterol accumulation may be via increased miR-122 inhibition of Cyp7a1, causing decreased cholesterol catabolism to bile acids. [score:3]
Further, we hypothesized that inhibiting miR-122 would normalize the IUGR- and maternal HFD -induced increase in cholesterol and decrease in Cyp7a1 protein. [score:3]
Injection of a miR-122 inhibitor increased hepatic Cyp7a1 protein levels (Figure 3B) and decreased hepatic cholesterol levels (Figure 3C) in IUGR+HFD female rats. [score:3]
Semi-quantitative Real-time RT PCR quantification was performed using miR-103 as an internal control, since C [t] values of miR-103 did not differ between intrauterine conditions or after administration of miR-122 inhibitor, mimic, or scrambled sequence. [score:3]
Our study design resulted in 4 groups: Con+HFD rats injected with a scrambled sequence as a control (CH+Scr), Con+HFD rats injected with a miR-122 mimic (CH+Mim), IUGR+HFD rats injected with a scrambled sequence as a control (IH+Scr), and IUGR+HFD rats injected with a miR-122 inhibitor (IH+Inh). [score:3]
Inhibition of miR-122 in IUGR+HFD rats partially increased Cyp7a1 protein and decreased hepatic cholesterol levels, suggesting that miR-122 plays a role in hepatic cholesterol accumulation in our rat mo del. [score:3]
A scrambled sequence of miR-122 was used as a negative control, designed with the same oligonucleotides as the miR-122 mimic but in a different order, and is thus unable to inhibit or mimic the function of miR-122 (Applied Biosystems). [score:3]
While a 2.5 mg/kg dose of a miR-122 inhibitor was able to normalize Cyp7a1 protein, a larger dose of the miR-122 mimic may have been needed to replicate IUGR+HFD pathophysiology in our rat mo del. [score:3]
miR-122 is a unique molecule with great potential in diagnosis, prognosis of liver disease, and therapy both as miRNA mimic and antimir. [score:3]
Regulation of Cyp7a1 also occurs via post-transcriptional regulation by microRNAs such as miR-122 (Song et al., 2010). [score:3]
Inhibition of miR-122 in IUGR+HFD female rats increased Cyp7a1 protein and decreased hepatic cholesterol in IUGR+HFD rats. [score:3]
HFD fed IUGR and control offspring were injected with a microRNA-122 mimic, inhibitor, or scrambled sequence to test the function of miR-122 in hepatic cholesterol accumulation in this mo del. [score:3]
FIGURE 3Injection of a miR-122 inhibitor into IUGR+HFD female rats decreased hepatic miR-122 (A), increased Cyp7a1 protein (B), and decreased hepatic cholesterol (C). [score:3]
Inhibition of miR-122 decreased hepatic cholesterol and increased Cyp7a1 protein levels in IUGR+HFD female rats, suggesting that IUGR and maternal HFD -induced hepatic cholesterol accumulation occurs in part through increased hepatic miR-122. [score:3]
Compared to injection of miR-122 scrambled sequence as a control, injection of a miR-122 mimic to Con+HFD female rats increased hepatic miR-122 levels and administration of a miR-122 inhibitor to IUGR+HFD female rats decreased miR-122 levels (Figure 3A). [score:2]
MicroRNA-122 mimic, inhibitor, or scrambled sequence were administered via a single injection into a betadine and ethanol sterilized tail vein for a total dose of 2.5 mg/kg body weight. [score:2]
Inhibition of MicroRNA-122 Increased Cyp7a1 Protein and Decreased Hepatic Cholesterol in IUGR Rats Exposed to a Maternal HFD. [score:2]
Con+HFD rats were injected with a miR-122 mimic to test the function of miR-122 in developing the IUGR+HFD phenotype or with a miR-122 scrambled sequence as a control. [score:1]
Injection of a miR-122 mimic to Con+HFD female rats did not increase hepatic cholesterol or decrease hepatic Cyp7a1 protein. [score:1]
The primary finding in this study is that female rats subjected to IUGR and a maternal HFD had increased hepatic cholesterol, decreased hepatic Cyp7a1 protein and bile acids, and increased miR-122. [score:1]
In conclusion, female IUGR rats exposed to a maternal HFD had increased hepatic cholesterol accumulation, decreased hepatic Cyp7a1 protein, decreased hepatic bile acids, and increased hepatic miR-122. [score:1]
In Vivo miR-122 Experiments. [score:1]
However, we were unable to replicate IUGR+HFD rat cholesterol pathology with administration of a miR-122 mimic, suggesting the role of other pathways in inducing hepatic cholesterol accumulation in IUGR+HFD rats. [score:1]
In Vivo miR-122 Experiments The miR-122 mimic is a double-stranded oligonucleotide that mimics the function of endogenous miR-122 (Applied Biosystems). [score:1]
The miR-122 mimic is a double-stranded oligonucleotide that mimics the function of endogenous miR-122 (Applied Biosystems). [score:1]
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10
[+] score: 69
However, other studies found that the expression of miR-122 was downregulated in patients with severe fibrosis (SF) when compared with non-SF patients and controls, possibly through the upregulation of transforming growth factor beta 1 (TGF-b1)[41]. [score:8]
To confirm the results of the miRNA sequencing data, 4 upregulated miRNAs (rno-miR-122-5p, rno-miR-199a-5p, rno-miR-184 and rno-miR-202-5p) and 4 downregulated miRNAs (rno-miR-208a-3p, rno-miR-208a-5p, rno-miR-6314 and rno-miR-22-3p) were chosen to be further examined using real-time quantitative PCR. [score:7]
Among them, 12 miRNAs (rno-miR-10b-5p, rno-miR-122-5p, rno-miR-184, rno-miR-1843-5p, rno-miR-196c-5p, rno-miR-199a-5p, rno-miR-202-5p, rno-miR-206-3p, rno-miR-208b-5p, rno-miR-224-5p, rno-miR-298-5p and rno-miR-31a-5p) were significantly upregulated(p<0.01, fold-change >1) compared to the control group and only rno-miR-208a-3p were significantly downregulated (p<0.01, fold-change <-1) (Fig 3). [score:6]
Among the top 13 differentially expressed miRNAs, the five most abundantly expressed miRNAs were rno-miR-122-5p, rno-miR-184, rno-miR-31a-5p, rno-miR-199a-5p and rno-miR-208a-3p. [score:5]
Huang et at[40] found a potential role of miR-122-5p in cardiomyocyte apoptosis through Pax-8 knockout mice, which is consistent with our results that miR-122-5p expression increased in the late stage after infarction. [score:4]
The opposite trends and effects of miR-122-5p in heart failure further demonstrated the complexity of miRNA regulation in diseases, and the exact function depends on different pathogenesis process and pathological state. [score:4]
In addition, we also analyzed the expression patterns of 4 miRNAs, explored the regulatory functions of miR-122-5p and miR-184during the process of HF pathogenesis. [score:4]
To examine the effects of rno-miR-122-5p and rno-miR-184, cells were transfected with rno-miR mimics, rno-miR inhibitors, or scrambled controls (Guangzhou Ruibo biology Science & Technology Co,; Ltd; China). [score:3]
To further confirm the results of the miRNA sequencing and analyze the dynamic expression pattern of specific miRNAs in HF rats, the dynamic changes of miR-208a-3p (Fig 4B), miR-184 (Fig 4C), miR-122-5p (Fig 4D) and miR-199a-5p (Fig 4E) in the process of post-infarcted heart failure were analyzed. [score:3]
0160920.g005 Fig 5 (A) Relative expression levels of miR-122-5p and miR-184 after transfection. [score:3]
The expression of rno-miR-122-5p was barely changed at the early stage of post-MI, but markedly increased when overt HF developed. [score:3]
Differential profile and expression patterns of miRNAs in the rats mo del of post-infarction heart failure were found, and the pro-apoptotic roles of rno-miR-122-5p and rno-miR-184 were revealed. [score:3]
Time-course analysis revealed different expression patterns of 4 miRNAs: rno-miR-122-5p, rno-miR-199a-5p, rno-miR-184 and rno-miR-208a-3p. [score:3]
Huang et al[40] proved that miR-122 contributes to apoptosis in H9c2 cells through participating the apoptotic gene expression. [score:3]
We speculated that miR-122-5p participates in the heart failure progress via regulating apoptosis and could be a biomarker of heart failure. [score:2]
In addition, miR-122-5p and miR-184 have been reported to be involved in the regulation of apoptosis under particular conditions, so we speculated that these two miRNAs could play important roles in the pathogenesis of heart failure through apoptosis. [score:2]
Additionally, rno-miR-122-5p and rno-miR-184 were proved to promote apoptosis in vitro. [score:1]
Time course analysis of miR-208a-3p (B), miR-184 (C), miR-122-5p (D) and miR-199a-5p (E) were studied. [score:1]
The gain-of–function and loss-of-function experiments indicated that miR-122-5p transfection could significantly promote cardiomyocyte apoptosis with H [2]O [2] treatment (p<0.05) and even without H [2]O [2] challenging (p<0.05). [score:1]
Effect of rno-miR-122-5p and rno-miR-184 on cell apoptosis. [score:1]
In our results, we found the apoptotic role of miR-122-5p in both normal and H [2]O [2] treated H9c2 cells. [score:1]
Finally, gain- and loss-of-function experiments of rno-miR-122-5p and rno-miR-184 were analyzed in H [2]O [2] treated H9c2 cells. [score:1]
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11
[+] score: 62
We found that the expression levels of exosomal rno-miR-122-5p were significantly downregulated in the plasma and CSF of 10 min ischaemia rats compared with the sham controls and 5 min ischaemia rats. [score:5]
In conclusion, the differential expression of plasma exosomal miR-300-3p and miR-122-5p suggests that these two plasma exosomal miRNAs can be used as diagnostic markers for TIA in rat and as potential therapeutic targets. [score:5]
Although we found that the expression levels of exosomal rno-miR-122-5p and rno-miR-300-3p were significantly upregulated in the CSF of the 2 h ischaemia rats compared with the 10 min ischaemia rats, there were no significant differences in these exosomal miRNAs in the plasma, even though they showed an increasing trend. [score:5]
Based on the experimental data and analysis results, we can draw the following conclusion: compared with the expression in sham controls, the expression level of plasma exosomal rno-miR-122-5p was significantly decreased and there was no significant difference in the level of rno-miR-300-3p, or rno-miR-300-3p was significantly increased and there was no significant difference in the level of rno-miR-122-5p, we could speculate it is in the TIA; if both the rno-miR-122-5p and rno-miR-300-3p showed no significant difference, then, we could speculate it's not TIA. [score:4]
Previous reports have indicated that the miR-122-5p/miR-133b ratio could as a specific early prognostic biomarker for acute myocardial infarction (Cortez-Dias et al., 2016), and miR-122-5p upregulation can trigger the compensatory response of LPIN1 and CTDNEP1 in hepatosteatosis (Naderi et al., 2017). [score:4]
Two triacylglycerol pathway genes, ctdnep1 and lpin1, are down-regulated by hsa-mir-122-5p in hepatocytes. [score:4]
The exosomal rno-miR-122-5p levels were significantly downregulated in the plasma of 10 min ischaemia rats compared with the sham controls and 5 min ischaemia rats (P < 0.01, P < 0.05, respectively, Figure 7A). [score:3]
In our study, 2 miRNAs (rno-miR-122-5p and rno-miR-300-3p) were chosen from 39 candidate miRNAs that had common expression trends in CSF and plasma exosomes. [score:3]
Expression levels of exosomal rno-miR-122-5p in plasma and CSF. [score:3]
Recent evidence showed that miR-122-5p plays important roles in various human diseases. [score:3]
Figure 7Expression levels of plasma/CSF exosomal rno-miR-122-5p and rno-miR-300-3p in sham controls and the ischaemia groups (n = 5 each group; [*] P < 0.05, [#] P < 0.01, [&] P < 0.001). [score:3]
Finally, we identified two miRNAs (rno-miR-122-5p and rno-miR-300-3p) that had common expression trends in CSF and plasma exosomes and had significant differences between the sham group and ischaemia group (5 or 10 min). [score:3]
We analyzed the expression levels of plasma exosomal rno-miR-122-5p and rno-miR-300-3p in rats after episodes of brief focal cerebral ischaemia (5 and 10 min) compared with IS (2 h) and sham controls. [score:2]
Among various miRNAs, miR-122-5p is also an inflammation-related miRNA that plays an important role in the pathogenesis of dyslipidaemia and apoptosis (Hromadnikova et al., 2015; Liu et al., 2016) and is positively correlated with the regulation of NFκB and inflammatory activity (Matsuura et al., 2016; Weaver et al., 2016). [score:2]
When the expression in the 10 min ischaemia group was compared to that in the sham controls, the AUC for the plasma exosomal rno-miR-122-5p was 0.960 (95%CI: 0.843-1.000, Figure 9B). [score:2]
Further studies and analysis of miR-300-3p and miR-122-5p are needed. [score:1]
Circulating mir-122-5p/mir-133b ratio is a specific early prognostic biomarker in acute myocardial infarction. [score:1]
All the above results suggest that plasma exosomal rno-miR-122-5p and rno-miR-300-3p are promising biomarkers for diagnosing TIA in rats. [score:1]
Figure 8Correlation between the plasma and CSF of levels of exosomal rno-miR-122-5p (A) (R = 0.632, P < 0.005), rno-miR-300-3p (B) (R = 0.719, P < 0.001). [score:1]
In addition, miR-122-5p plays a role in the pathophysiology of heart failure (Marques et al., 2016). [score:1]
Figure 9Diagnostic value of plasma exosomal rno-miR-122-5p and rno-miR-300-3p in rats. [score:1]
We hypothesized that the plasma rno-miR-300-3p and rno-miR-122-5p, which were derived from CSF, were reduced by the BBB (Sørensen et al., 2014). [score:1]
However, there is no information available regarding miR-122-5p in TIA. [score:1]
Spearman's correlation test was used to analyse correlations between the plasma and CSF of exosomal rno-miR-122-5p and rno-miR-300-3p. [score:1]
These findings suggested that plasma exosomal rno-miR-300-3p and rno-miR-122-5p are very valuable for diagnosing TIA in rats. [score:1]
In summary, we demonstrated that both miR-122-5p and miR-300-3p are related to cerebral ischaemic injury. [score:1]
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[+] score: 50
The results of the present study showed that crocin pretreatment (1) protected the rat's liver against hepatic IR -induced injury; (2) upregulated the protein expression of Nrf2; (3) downregulated the expression levels of miR-122 and miR-34a; (4) improved the liver enzymes AST, ALT, and ALP; (5) increased the antioxidant activity of SOD, GPx, and CAT; and (6) decreased the protein expression of p53 following hepatic IR -induced injury. [score:13]
The results of the current study showed that crocin (a) decreased the increased serum levels of miR-122 and miR-34a in rats following IR -induced injury; (b) downregulated the protein expression of p53 in the liver; (c) decreased the increased serum levels of liver enzymes; (d) increased the decreased level of antioxidant activity of SOD, GPx, and CAT in the liver; (e) mitigated the histopathological changes induced by hepatic IR injury; and (f) increased Nrf2 expression. [score:8]
The findings of the present study showed that crocin as a potent antioxidant through downregulating miR-122 and miR-34a effectively controls ROS -induced liver injury. [score:4]
Miravirsen has been shown to treat HCV infection through functionally inhibiting miR-122 [71]. [score:3]
Therefore, it seems that this effect of crocin pretreatment on the level of miR-122 expression could be secondary to its cytoprotective activity as demonstrated by histopathological findings. [score:3]
The present findings also showed that crocin pretreatment decreased the overexpression of miR-122 induced by IR injury. [score:3]
miR-122 has been shown to exert several effects in liver such as development, hepatic function [8], and hepatocyte growth [9]. [score:2]
Effect of Hepatic IR Injury and Crocin Pretreatment on the Serum Levels of miR-122 and miR-34a. [score:1]
Our qRT-PCR results showed that the serum level of miR-122 enhanced after IR -induced liver injury. [score:1]
The qRT-PCR results showed that the serum levels of miR-122 in Cr + IR rats were significantly decreased but it was still higher than that in the sham group. [score:1]
As evidenced by the current histopathological and qRT-PCR results, there is a close correlation between the serum level of miR-122 and severity of liver tissue damage. [score:1]
miR-122, a 22-nucleotide microRNA, is derived from a RNA transcript from the gene hcr in the liver cells. [score:1]
There is not any report about the effect of crocin on serum levels of miR-122. [score:1]
Therefore, these findings taken together suggest that the monitoring of the serum level of miR-122 could be a high sensitive, early, accurate, and reliable biomarker for determining the progression of liver injuries. [score:1]
As demonstrated in Figures 3(a) and 3(b), according to qRT-PCR results, the serum levels of miR-122 and miR-34a were significantly increased following hepatic IR injury. [score:1]
In the sham group, the levels of miR-122 and miR-34a were minimal (P < 0.001 in both cases). [score:1]
A previous report showed that there is a close correlation between the serum level of miR-122 and enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) following warm IR -induced liver injury in rats [11]. [score:1]
These levels are the most common parameters which have been applied to manage the hepatic injury [13], while recent studies have demonstrated that miR-122 is a more sensitive parameter in hepatic injury [14, 15]. [score:1]
It is well known that miR-122 is a noninvasive and early releasing circulating biomarker for determination of hepatic disorders [10]. [score:1]
The serum level of hepato-specific miR [miR-122] has been shown to increase faster than the serum concentrations of ALT and AST enzymes following hepatic IR injury [51]. [score:1]
Our results also showed that the highest and lowest levels of miR-122 were, respectively, observed in IR and sham groups. [score:1]
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13
[+] score: 42
Almost all the up-regulated miRNAs (22 our of 25 miRNAs) such as miR-122, miR-192, miR-685, miR-193, and miR-29c were also up-regulated in our rat mo del, suggesting that common plasma miRNAs seem to be up-regulated in APAP -induced liver injury independent of species. [score:10]
In addition, it has been reported that ALT is mainly expressed in the portal vein area [19], whereas our preliminarily study revealed that the miR-122 uniformly shows high expression in liver at the pericentral and periportal regions (unpublished data). [score:5]
We chose miR-16, miR-21 and miR-122 because their sequences are identical in rat and human and these miRNAs are substantially expressed in plasma. [score:3]
Thus, as represented by miR-122, the profile of miRNA expression could serve as a tool for understanding the onset and progression of liver injury. [score:3]
The ALT and miR-122 levels began to increase 3 h after the administration, but the extent and rate of the increase of miR-122 was more dramatic than those of the ALT levels (Fig. 5B). [score:1]
Moreover, we showed that the plasma miR-122 level was quantitatively correlated with the extent of histopathologic changes (Fig. 6). [score:1]
Among them, we focued on miR-122, which is the most abundant miRNA in liver [21], in the next experiment. [score:1]
In addition, the extent of the increase of miR-122 mirrored the histopathological changes (++ 15.2 and +++ 20.0±1.5). [score:1]
Association of plasma miR-122 level with hepatocellular injury. [score:1]
The miR-21 and miR-122 were decreased to 2% and 1% of the control, respectively, after 6 h incubation at 37°C, whereas the miR-16 was sustained at 30% of the control. [score:1]
Stability of miR-16, miR-122 or miR-21 in rat (A) or human (B) plasma. [score:1]
Time -dependent changes of plasma ALT and miR-122 levels in individual rat orally administered 1000 mg/kg of APAP (n = 6) with fasting (A) or 300 mg/kg MP (n = 5) (B). [score:1]
In the 7 rats showing mild (+) histopathological changes, the increase of the ALT levels was not significant (104±107, 3.1 fold of control), but the increase of the miR-122 level was remarkable (10.6±1.0, 11.3 fold of control). [score:1]
Although there were large interindividual differences in the ALT levels, the interindividual differences in plasma miR-122 level were relatively small. [score:1]
Subsequently, it was reported that the plasma miR-122 level was increased in a rat mo del of hepatocellular injury caused by trichlorobromomethane or carbon tetrachloride (CCl [4]) administration [13], and was increased in a mouse mo del of D-galactosamine/lipopolysaccharides- or alcohol -induced liver injury [14]. [score:1]
Therefore, we could conclude that the increase of the plasma miR-122 was due to liver injury, but not to APAP itself. [score:1]
The level of miR-122 was 10-fold higher than the levels of miR-16 and miR-21, which showed similar levels. [score:1]
It should be noted that the change of plasma miR-122 was more dynamic than that of ALT. [score:1]
The miR-122 levels represent relative value to control. [score:1]
That might be another reason for the more sensitive response of miR-122 than ALT toward the liver injury which would be a benefit as a biomarker. [score:1]
In these rats, the plasma miR-122 levels were almost the same as those in control rats (40-Ct value: 7.1±2.6 versus 7.1±1.6 in control). [score:1]
In contrast, the plasma miR-122 levels began to increase 3 h after the administration, reached a peak at 12–36 h and then decreased. [score:1]
We examined whether the increase of plasma miR-122 was due to liver injury or the administered chemicals. [score:1]
We examined the time course of the plasma miRNA changes in rats with acute liver injury, focusing on miR-122. [score:1]
Association of the plasma miR-122 increase with hepatocellular injury. [score:1]
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[+] score: 42
0037395.g003 Figure 3(A) Serum miR-122 expression levels; (B) Serum miR-192 expression levels; (C) Serum miR-193 expression levels; (D) Biochemical parameter: serum ALT levels; (E) Biochemical parameter: serum AST levels. [score:7]
0037395.g004 Figure 4(A) Serum miR-122 expression levels; (B) Serum miR-192 expression levels; (C) Serum miR-193 expression levels; (D) Biochemical parameter: serum ALT levels; (E) Biochemical parameter: serum AST levels; The absolute concentrations of target miRNAs were calculated by referring to calibration curves developed with corresponding synthetic miRNA oligonucleotides. [score:7]
Among them, circulating miR-122 had been reported as liver-specifically conserved across species [24], [35], [36] and has been applied to diagnosis of various liver diseases in clinical studies, including hepatocellular carcinoma (HCC) [38], [39], [40], hepatitis B virus (HBV) infection [24], [39], cirrhosis [38] and alcohol- and chemical-related hepatic diseases [24], [27]. [score:5]
Unfortunately, this approach has its own disadvantages; circulating miR-122 could not serve as a biomarker to distinguish these different liver diseases. [score:3]
Once an elevated circulating miR-122 level has been detected, a physician cannot make a judgment about what the specific liver disease(s) is/are using this information alone. [score:3]
By individual TaqMan qRT-PCR analysis of dysregulated serum miRNAs uncovered by serum TLDA and dysregulated liver tissue miRNAs uncovered by microarray hybridization in primary screening, 6 serum miRNAs, including miR-122, miR-192, miR-193, miR-200a, miR-21 and miR-29c, exhibited a high correlation with primary screening results. [score:3]
Beside, among the three serum miRNAs as potential diagnostic biomarker for DILI explored in rat mo dels in present study, miR-122 and miR-192 was also validated in plasma of mice mo dels by Wang et al. [27]. [score:1]
Besides, unlike ALT and AST, miR-122 has no association with muscle disorders [24]. [score:1]
In the dose -dependent analysis of the serum miRNAs miR-122, miR-192 and miR-193, miR-122 showed extremely high sensitivity in both 2 DILI mo del groups (fold change >50.0), while serum biochemical parameters (e. g., ALT and AST) displayed only mild sensitivity (fold change <20.0) in the high-dose group. [score:1]
Patients with circulating miR-122 elevation might be infected by HBV and/or present HCC and/or be stimulated by alcohol abuse rather than drug overdosing. [score:1]
The panel of aberrantly expressed serum miRNAs (miR-122, miR-192 and miR-193) all exhibited time- and dose -dependent characteristics. [score:1]
Our results demonstrate that a new panel of serum miRNAs (miR-122, miR-192 and miR-193) could have the potential to serve as sensitive, specific and noninvasive biomarkers for the diagnosis of DILI. [score:1]
The concentration of serum miR-122 peaked at 12 h after administration (fold change >100.0), while serum biochemical parameters showed a limited change (fold change <3.0). [score:1]
The liver-specific miR-122, for example, is over 1,000 times more abundant in 0.1 g liver tissue than in 0.1 mL serum (Figure S3). [score:1]
Among this set of serum miRNAs, miR-122, miR-192 and miR-193 presented a significant change in both DILI mo del groups within the threshold of a fold change >10 and P-value<0.05 (Table 1). [score:1]
Previously, plasma miR-122 and miR-192 had been reported increased linearly from 1 to 3 hours and displayed dose -dependent manner after APAP overdosing in mice. [score:1]
All 3 serum miRNAs demonstrated better sensitivity than serum biochemical parameters in the middle- and low-dose group, but serum miR-122 was much more sensitive than biochemical parameters (Figure 4A, 4B, 4C, 4D and 4E). [score:1]
In summary, serum miR-122, miR-192 and miR-193 constitute a new panel for compound- and herb -induced liver injury diagnosis. [score:1]
Given that circulating miR-122 was previously reported as a DILI biomarker, the results from the strategies in this study indicate that there is a set of serum miRNAs highly related to DILI. [score:1]
In the time -dependent analysis of the serum miRNAs miR-122, miR-192 and miR-193, all of these serum miRNAs exhibited an ascending trend 3 h after administration in both DILI mo del groups (fold change >2.0); while serum biochemical parameters (e. g., ALT and AST) remained at baseline levels (fold change <1.5). [score:1]
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15
[+] score: 33
The results demonstrated that in the hypertonic dialysate group, miR-31, miR-93, miR-100, miR-152, miR-497, miR-192, miR-194 and miR-200b were all significantly down-regulated whereas miR-122 was highly up-regulated (all P <0.05) (Figure  3). [score:7]
The miRNA screen identified 8 significantly down-regulated miRNAs (miR-31, miR-93, miR-100, miR-152, miR-497, miR-192, miR-194 and miR-200b) and one highly up-regulated miRNA (miR-122) in the hypertonic dialysate group. [score:7]
Compared with the control and saline groups, both miRNA microarray and real-time PCR analyses demonstrated that miR-31, miR-93, miR-100, miR-152, miR-497, miR-192, miR-194 and miR-200b were significantly down-regulated, and miR-122 was highly up-regulated in the hypertonic dialysate group. [score:6]
miR-122 is the only miRNA identified to be significantly up-regulated in our rat mo del of hypertonic dialysate -induced peritoneal fibrosis. [score:4]
Studies of miR-122 in other tissues or disease mo dels are extremely limited. [score:3]
Significantly increased expression of miR-122 was observed in the hypertonic dialysate group compared with the saline and control groups (Table  3). [score:2]
The results suggest that miR-122 may contribute to the regulation of tissue remo deling, collagen production and pathogenesis of diet- or hepatitis C virus -induced liver fibrosis [48- 50]. [score:2]
Our result provides additional evidence supporting the role of miR-122 in fibrogenesis. [score:1]
As the most abundant miRNA species in hepatocytes, the role of miR-122 in fibrogenesis has been well studied in liver mo dels. [score:1]
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[+] score: 32
miRNAs have been associated with and put forth as putative biomarkers of human disease, including hepatitis C (miR-122) [6], cardiovascular diseases (miR-192) [7] and various types of cancers [8]. [score:5]
While the sensitivity of miR-122 versus ALT has not been definitively determined in any species, these collective studies indicate that miR-122 is a translatable diagnostic to detect liver injury [61]. [score:3]
Non-liver enriched miRNAs were not elevated or were found to be in the noise or below the lower limit of Q-RT-PCR detectionElevation of miR-122 in the plasma/serum after administration of hepatotoxic compounds in rats [58, 59] or in various human disease conditions [19, 60] is well established. [score:3]
Q-RT-PCR ΔCt values (y-axis) line plot per animal for duration of Day 1, 7, and 14 treatment samples tested highlights the elevation of both liver enriched miRNAs (miR-122 and miR-885) and ubiquitously expressed miR-193 in the 2 dogs with elevated ALT and AST. [score:3]
Non-liver enriched miRNAs were not elevated or were found to be in the noise or below the lower limit of Q-RT-PCR detection Elevation of miR-122 in the plasma/serum after administration of hepatotoxic compounds in rats [58, 59] or in various human disease conditions [19, 60] is well established. [score:3]
Serum was also analyzed by Q-RT-PCR for a panel of 20 tissue enriched and potential miRNA biomarkers, including those identified for liver (cfa-miR-122 and -885), heart/muscle (cfa-miR-1, -133, and -206), testis (miR-34b/c), pancreas (cfa-miR-216), brain (cfa-miR-212), and ubiquitously expressed cfa-miR-193b. [score:3]
Dogs 1 and 3 had high correlation between elevations in serum miR-122 and ALT (r [2] = 0.79) and AST (r [2] = 0.90) levels while elevations in serum miR-885 were higher ALT (r [2] = 0.87) and AST (r [2] = 0.97). [score:1]
The results from these two POC studies represent the first published data demonstrating the utility of miR-122 and miR-885 as potential biomarkers of liver injury in the dog. [score:1]
The two liver HTE miRNAs in dogs were miR-122 and the reverse complement miR-3591 (Fig.   3). [score:1]
Taken together, these results highlight the specificity of miR-122 and miR-885 for compound -induced liver injury. [score:1]
Additionally, Dog 3 demonstrated elevated miR-122 on Day 7 at the 24 h time point while ALT remained at baseline levels. [score:1]
Elevations in liver enriched miR-122 and miR-885 correlated with increases in ALT and AST (Fig.   6a and b) and mild to moderate hepatocellular necrosis was observed in 2 of 6 animals (Dogs 1 and 3 on Day 14 [data not shown]). [score:1]
In the literature, miR-122 is liver specific for mice, rats, and humans and has been used as a biomarker for liver injury [5, 10, 12]. [score:1]
However, there are examples of validated biomarkers such as miR-122, which is detectable in the blood after liver injury in mice, rats, dogs and humans [9, 17– 20]. [score:1]
Dogs with elevated serum levels of miR-122 and miR-885 had a correlative increase of alanine aminotransferase, and microscopic analysis confirmed liver damage. [score:1]
A total of 22 miRNAs (Additional file 6: Figure S5) were selected for qPCR validation including the following 14 biomarker candidates of organ toxicity: liver (cfa-miR-122 and -885), pancreas (cfa-miR-216a/b); heart (cfa-miR-499); muscle (cfa-miR-206); heart/muscle (cfa-miR-1, -133a/b, and -208); testis (cfa-miR-34b/c); and brain and sciatic nervous tissues (cfa-miR-212, -432, and -885), and 5 miRNAs reported in the literature (cfa-miR-21, -192, -193a/b, and -200). [score:1]
This is consistent with a previous rat study that detected an increase in miR-122 levels prior to ALT elevation [58]. [score:1]
Levels of miR-122 increased in correlation with minimal liver injury in the absence of ALT elevations, and thus may have superior sensitivity than standard liver function tests. [score:1]
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[+] score: 31
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]
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]
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]
These results suggest that elevated miR-122 expression is an early event in the pathogenesis of HBV infection. [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]
Moreover, the level of plasma miR-122 exhibits an excellent correlation with the necro-inflammatory activity of HBV [34] and HCV infection [35, 36]. [score:1]
The ROC curve area for the combination of miR-27a and miR-122 was 0.94 (Figure 3F). [score:1]
The serum miR-122 level was also markedly higher in the CHB group than in the HBC group (P<0.0001). [score:1]
Serum levels of miR-27a and miR-122 in CHB, HBC and Ctrl subjects. [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]
Serum levels of miR-27a and miR-122 in a rat mo del of liver cirrhosis induced by DMN and saline. [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]
Additionally, miR-122 was previously described to be a liver-specific miRNA [32]. [score:1]
We conclude that circulating miR-27a may be a more specific predictor for HBC than miR-122. [score:1]
Moreover, miR-122 level in CHB patients were higher than those in HBC subjects (P<0.0001) (Figure 2B). [score:1]
The serum miR-122 level was significantly higher in the HBC and CHB groups than in the Ctrl group (P<0.0001 for both). [score:1]
In rodents, liver injury induced by alcohol or chemicals increases the level of serum or plasma miR-122, and this increase occurs earlier than the increase in ALT, a commonly used marker [13, 33]. [score:1]
Additionally, serum miR-122 was considerably higher in HBC patients than in Ctrl subjects (P<0.0001). [score:1]
MiR-122 was also detected, which has been described as a liver-specific miRNA that exhibits an excellent correlation with hepatitis B virus infection, cholesterol metabolism and HCC [11, 13, 14]. [score:1]
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[+] score: 29
Other miRNAs from this paper: hsa-mir-34a, hsa-mir-122, rno-mir-34a, hsa-mir-455, rno-mir-455
However, the expression of this miRNA was nonsignificant in dose as well as time groups during differential expression analysis (Fig.   6), suggesting that miR-122 may not be directly involved in the mechanism of TAA -mediated hepatotoxicity in liver tissue. [score:6]
On the other hand, miR-122 has been extensively studied and keen interest was expressed as a promising circulating biomarker in liver disease 44– 46. [score:5]
From the top, the logFC expression of rno-miR-122-5p is not significantly differentially expressed when compared with control animals. [score:4]
Even though abundant rno-miR-122 was consistently expressed over each treatment condition in this study, there was no differential expression of rno-miR-122 compared to the concurrent control animals at neither time nor dose, indicating a lack of the relevance to effects associated with the treatment. [score:4]
Surprisingly, miR-122, which is a commonly studied circulating miRNA biomarker for liver injury, was not differentially expressed according to neither dose nor time point in the liver tissues treated with TAA. [score:3]
Taking the consideration of lack of mechanistic relevance to the treatment regardless the abundant expression in the rat livers of rno-miR-122, it could serve as a house-keeping miRNA for the liver. [score:3]
Expression of miR-34a-5p, miR-455-3p and miR-122. [score:3]
The rno-miR-122 was found as one of the top ten most abundant miRNAs in the livers across all the treatment. [score:1]
[1 to 20 of 8 sentences]
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[+] score: 25
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-mir-18a, hsa-mir-21, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-30a, hsa-mir-99a, hsa-mir-103a-2, hsa-mir-103a-1, mmu-mir-1a-1, mmu-mir-23b, mmu-mir-30a, mmu-mir-99a, mmu-mir-126a, mmu-mir-9-2, mmu-mir-133a-1, mmu-mir-138-2, hsa-mir-192, mmu-mir-204, mmu-mir-122, hsa-mir-204, hsa-mir-1-2, hsa-mir-23b, hsa-mir-122, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-138-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-126, hsa-mir-138-1, mmu-mir-192, mmu-let-7a-1, mmu-let-7a-2, mmu-mir-18a, mmu-mir-21a, mmu-mir-23a, mmu-mir-26a-1, mmu-mir-103-1, mmu-mir-103-2, hsa-mir-1-1, mmu-mir-1a-2, mmu-mir-26a-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-138-1, hsa-mir-26a-2, hsa-mir-376c, hsa-mir-381, mmu-mir-381, mmu-mir-133a-2, rno-let-7a-1, rno-let-7a-2, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-18a, rno-mir-21, rno-mir-23a, rno-mir-23b, rno-mir-26a, rno-mir-30a, rno-mir-99a, rno-mir-103-2, rno-mir-103-1, rno-mir-126a, rno-mir-133a, rno-mir-138-2, rno-mir-138-1, rno-mir-192, rno-mir-204, mmu-mir-411, hsa-mir-451a, mmu-mir-451a, rno-mir-451, hsa-mir-193b, rno-mir-1, mmu-mir-376c, rno-mir-376c, rno-mir-381, hsa-mir-574, hsa-mir-652, hsa-mir-411, bta-mir-26a-2, bta-mir-103-1, bta-mir-16b, bta-mir-18a, bta-mir-21, bta-mir-99a, bta-mir-126, mmu-mir-652, bta-mir-138-2, bta-mir-192, bta-mir-23a, bta-mir-30a, bta-let-7a-1, bta-mir-122, bta-mir-23b, bta-let-7a-2, bta-let-7a-3, bta-mir-103-2, bta-mir-204, mmu-mir-193b, mmu-mir-574, rno-mir-411, rno-mir-652, mmu-mir-1b, hsa-mir-103b-1, hsa-mir-103b-2, bta-mir-1-2, bta-mir-1-1, bta-mir-133a-2, bta-mir-133a-1, bta-mir-138-1, bta-mir-193b, bta-mir-26a-1, bta-mir-381, bta-mir-411a, bta-mir-451, bta-mir-9-1, bta-mir-9-2, bta-mir-376c, bta-mir-1388, rno-mir-9b-3, rno-mir-9b-1, rno-mir-126b, rno-mir-9b-2, hsa-mir-451b, bta-mir-574, bta-mir-652, mmu-mir-21b, mmu-mir-21c, mmu-mir-451b, bta-mir-411b, bta-mir-411c, mmu-mir-126b, rno-mir-193b, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
The expression analysis of selected miRNAs using qRT-PCR also showed that miR-26a and -99a were highly expressed in all tissues, while miR-122 and miR-133a were predominantly expressed in liver and muscle, respectively. [score:7]
The expression profiles of the 11 miRNAs across 11 tissues confirmed that miR-26a and -99a expressed at high levels in all tissues, while miR-122 and -133a exclusively expressed in liver and muscle, respectively. [score:7]
Comparison of miRNA expression profiles among tissues revealed that very few miRNAs expression was tissue specific (e. g., miR-9, -124 in brain, miR-122 in liver, miR-1, miR-133a and -206 in muscle). [score:5]
Our comparison of miRNA expression across 11 tissues from bovine revealed a few tissue specific miRNAs: miR-9, -124 in brain, miR-122 in liver, miR-1, miR-133a and -206 in muscle, which had been previously reported in mouse and human [13, 27]. [score:3]
To validate above miRNA expression patterns, quantitative RT-PCR was performed on tissue-specific miRNAs (miR-122, -133a), high cloning frequency miRNAs (miR-26a, -99a and -150) and low cloning frequency miRNAs (miR-103, -107, -411, -423-5p, -574-3p and -652). [score:3]
[1 to 20 of 5 sentences]
20
[+] score: 25
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-20a, hsa-mir-22, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-98, hsa-mir-101-1, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-15b, mmu-mir-101a, mmu-mir-126a, mmu-mir-130a, mmu-mir-133a-1, mmu-mir-142a, mmu-mir-181a-2, mmu-mir-194-1, hsa-mir-208a, hsa-mir-30c-2, mmu-mir-122, mmu-mir-143, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-181a-1, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-122, hsa-mir-130a, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-142, hsa-mir-143, hsa-mir-126, hsa-mir-194-1, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-208a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-18a, mmu-mir-20a, mmu-mir-22, mmu-mir-26a-1, mmu-mir-26b, mmu-mir-29c, mmu-mir-98, mmu-mir-326, rno-mir-326, rno-let-7d, rno-mir-20a, rno-mir-101b, mmu-mir-101b, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-181b-2, mmu-mir-17, mmu-mir-19a, mmu-mir-181a-1, mmu-mir-26a-2, mmu-mir-19b-1, mmu-mir-181b-1, mmu-mir-181c, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-101-2, hsa-mir-26a-2, hsa-mir-378a, mmu-mir-378a, hsa-mir-326, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-181b-2, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-15b, rno-mir-16, rno-mir-17-1, rno-mir-18a, rno-mir-19b-1, rno-mir-19a, rno-mir-22, rno-mir-26a, rno-mir-26b, rno-mir-29c-1, rno-mir-30c-1, rno-mir-30c-2, rno-mir-98, rno-mir-101a, rno-mir-126a, rno-mir-130a, rno-mir-133a, rno-mir-142, rno-mir-143, rno-mir-181c, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-194-1, rno-mir-194-2, rno-mir-208a, rno-mir-181a-1, hsa-mir-423, hsa-mir-18b, hsa-mir-20b, hsa-mir-451a, mmu-mir-451a, rno-mir-451, ssc-mir-122, ssc-mir-15b, ssc-mir-181b-2, ssc-mir-19a, ssc-mir-20a, ssc-mir-26a, ssc-mir-326, ssc-mir-181c, ssc-let-7c, ssc-let-7f-1, ssc-let-7i, ssc-mir-18a, ssc-mir-29c, ssc-mir-30c-2, hsa-mir-484, hsa-mir-181d, hsa-mir-499a, rno-mir-1, rno-mir-133b, mmu-mir-484, mmu-mir-20b, rno-mir-20b, rno-mir-378a, rno-mir-499, hsa-mir-378d-2, mmu-mir-423, mmu-mir-499, mmu-mir-181d, mmu-mir-18b, mmu-mir-208b, hsa-mir-208b, rno-mir-17-2, rno-mir-181d, rno-mir-423, rno-mir-484, mmu-mir-1b, ssc-mir-15a, ssc-mir-16-2, ssc-mir-16-1, ssc-mir-17, ssc-mir-130a, ssc-mir-101-1, ssc-mir-101-2, ssc-mir-133a-1, ssc-mir-1, ssc-mir-181a-1, ssc-let-7a-1, ssc-let-7e, ssc-let-7g, ssc-mir-378-1, ssc-mir-133b, ssc-mir-499, ssc-mir-143, ssc-mir-423, ssc-mir-181a-2, ssc-mir-181b-1, ssc-mir-181d, ssc-mir-98, ssc-mir-208b, ssc-mir-142, ssc-mir-19b-1, hsa-mir-378b, ssc-mir-22, rno-mir-126b, rno-mir-208b, rno-mir-133c, hsa-mir-378c, ssc-mir-194b, ssc-mir-133a-2, ssc-mir-484, ssc-mir-30c-1, ssc-mir-126, ssc-mir-378-2, ssc-mir-451, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, mmu-mir-378b, mmu-mir-101c, hsa-mir-451b, hsa-mir-499b, ssc-let-7a-2, ssc-mir-18b, hsa-mir-378j, rno-mir-378b, mmu-mir-133c, mmu-let-7j, mmu-mir-378c, mmu-mir-378d, mmu-mir-451b, ssc-let-7d, ssc-let-7f-2, ssc-mir-20b-1, ssc-mir-20b-2, ssc-mir-194a, mmu-let-7k, mmu-mir-126b, mmu-mir-142b, rno-let-7g, rno-mir-15a, ssc-mir-378b, rno-mir-29c-2, rno-mir-1b, ssc-mir-26b
Expression analysis of conserved miRNAs in 14 different tissue types revealed heart-specific expression of miR-499 and miR-208 and liver-specific expression of miR-122. [score:7]
Thus, miRNA families (e. g., miR-1 and miR-122) that are specifically or highly expressed in any one of the 3 tissues, or miRNAs that are expressed ubiquitously (e. g., let-7 and miR-26) in all 3 tissues, show a far greater frequency than other miRNAs. [score:5]
We also found miR-194 abundantly expressed in the liver, and its level of expression was comparable with that of miR-122 (Figure 2B). [score:5]
Several miRNAs (miR-1, miR-133, miR-499, miR-208, miR-122, miR-194, miR-18, miR-142-3p, miR-101 and miR-143) have distinct tissue-specific expression patterns. [score:3]
We observed specific and abundant expression of miR-122 in the liver (Figure 3B). [score:3]
A similar picture has emerged for miR-122, a liver-specific miRNA and one of the highly represented miRNAs in our sequences. [score:1]
As another example, miR-122 is represented by 126 reads (Table 1). [score:1]
[1 to 20 of 7 sentences]
21
[+] score: 22
Other miRNAs from this paper: rno-mir-16, rno-mir-103-2, rno-mir-103-1, rno-mir-191a, rno-mir-191b
This observation is in accordance with the diminished expression of its negative regulator miR-122 in AA -treated livers and is in agreement with previous data showing an inverse correlation between miR-122 and CCNG1 expression [42]. [score:6]
In order to evaluate some of the normalization methods analyzed in this report, we studied the liver expression of miR-122 and its validated mRNA target, Cyclin G1 (CCNG1) [42], in AA treated rats, using the same experimental design used to confirm the altered expression of RGs. [score:5]
When we normalized the miR-122 expression levels using RNU48, a candidate microRNA RG with a lower expression stability, we still observed a significant change in AA -treated rats (C 1.00±0.24 vs. [score:5]
We determined the expression level of miR-122 by RT-qPCR using the two selected RGs (miR-16/5S) in the liver of AA -treated rats and, as expected, we observed a decrease in miR-122 levels (C 1.00±0.18 vs. [score:3]
Previous microarray analysis have shown that MicroRNA 122 (miR-122) diminishes its expression in AA -treated mouse livers 24 hours after toxic administration [41]. [score:3]
[1 to 20 of 5 sentences]
22
[+] score: 18
Importantly, while the expression of certain miRNAs was found to overlap across the two different populations (i. e., miR-122, miR-192 and Let-7a) the expression of other miRNAs was found to be differentially regulated. [score:6]
The analysis shows that liver-enriched miRNAs [miR-122 (P = 0.007) and miR-192 (P = 0.03)] are up-regulated at day 2 after PHx and the levels are reduced to almost pre-PHx levels (i. e., day 0) at days 4 and 6 after PHx (Fig. 6, top row). [score:4]
Interestingly, the liver specific miR-122 was found to be significantly up-regulated in activated HSCs following incubation with TGF-β1. [score:4]
It was found that the expression of miR-122 (P = 0.0001), miR-192 (P = 0.004), miR-194 (P = 0.03)] and Let-7a (P = 0.006) followed the same pattern as observed for vesicles -associated miRNAs (top rows in Figs 6 and 7), suggesting that these miRNAs do undergo comparable modulation in both fractions. [score:3]
Specifically, we found that the cytokines used in this study significantly increased levels of miR-122, miR-150, miR-21, miR-192 and miR-194 associated to EVs secreted from PCs. [score:1]
[1 to 20 of 5 sentences]
23
[+] score: 17
Our miRNA profiling study revealed that miR-122 expression is increased in plasma of ZDF rats during disease progression of T2D. [score:5]
In NASH patients and in animal mo dels, circulating miR-122 levels are elevated in serum, whereas its expression is decreased in liver tissue [43, 44]. [score:3]
The expression of miR-122 represented an exception reaching a peak already at β cell functional failure (approximately seven-fold elevation). [score:3]
miR-122 is considered to be a highly sensitive and specific biomarker in blood, reflecting hepatocyte injury, as increased levels of miR-122 were described in various liver diseases, such as non-alcoholic steatohepatitis (NASH) [42]. [score:2]
The strong increase of miR-122 is consistent with the fatty liver that ZDF rats develop when reaching their body weight plateau [45]. [score:1]
When β cell failure occurred, the circulating level of miR-133a remained high, and additionally, the level of miR-122 was significantly increased, whereas miR-203, miR-450a and miR-434-3p were decreased at this time point (Figure 4). [score:1]
Metformin leads to decreased circulating miR-140-5p (miR-140) and miR-122 levels in T2D patients [62]. [score:1]
miRNAs, such as miR-434-3p and miR-122, were specifically changed at the time point of β cell functional failure (Figure 4). [score:1]
[1 to 20 of 8 sentences]
24
[+] score: 16
Next, the expression of four endogenous miRNAs (miR-122, miR-192, miR-21 and miR-16) was analyzed by qPCR, showing that the detection of the analyzed targets sequence is linear (as shown by the linear regression R [2]). [score:5]
For highly abundant RNA targets (i. e. miR-122), the detection by qPCR maintains its linearity also when the input material is greatly diluted. [score:3]
Microarray analysis identified a panel of miRNAs, which are either highly expressed in the heart (miR-1, miR-133a and miR-16) or in the liver (miR-122, miR-192 and miR-194) or invariant (miR-21; Supplementary Figure 1a). [score:3]
As proof of principle, miRNA-specific primers targeting miR-122-5p, miR-122-3p and miR-21-5p were designed following the standard miQPCR design and without the additional 3′ end ‘G’ (for sequences see Supplementary Table 1a). [score:2]
Total RNA from heart or liver were reverse transcribed according to the miQPCR and TaqMan protocols and the expression of 7 miRNAs (miR-1, miR-133b, miR-16, miR-122, miR-194 and miR-21) and a small nuclear RNA (RNU6) was measured by qPCR with respectively SYBR-Green (top panel) or TaqMan probes (lower panel). [score:1]
Analysis of standard curves shows that endogenous miRNAs are detected over several orders of magnitude, while abundant miRNAs such as the liver specific miR-122 31 are detected from as little as 6 fg of cDNA. [score:1]
To identify whether miQPCR primer design is able to discriminate between mature miRNAs and their precursors miRNA-specific primers targeting miR-122-5p, miR-122-3p and miR-21-5p were designed according to the standard miQPCR design protocol (i. e. containing a 3′ end ‘G’ overlapping with the miLINKER) or without miLINKER overlap. [score:1]
[1 to 20 of 7 sentences]
25
[+] score: 13
Development of miRNA -targeted therapies such as miravirsen, which inhibits the hepatitis C virus by targeting liver-expressed miR-122 [32], give credence to the idea of using drugs targeting TBI-dysregulated miRNAs to improve survival of brain cells. [score:13]
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26
[+] score: 11
Mutational analysis and ectopic expression studies have revealed that miR-122 interacts with the 5' non-coding region of the viral genome [58]. [score:4]
This suggests that miR-122 may be a target for antiviral interaction [58]. [score:3]
In addition, miR-122 is a key regulator of cholesterol and fatty-acid metabolism in the adult liver by regulating plasma cholesterol levels, fatty-acid oxidation, hepatic fatty-acid synthesis as well as cholesterol synthesis [22]. [score:3]
The liver-specific miRNA, miR-122, likely modulates the hepatitis C virus by facilitating replication of the viral RNA. [score:1]
[1 to 20 of 4 sentences]
27
[+] score: 10
For liver cancer, one recent study reported that miR-21, miR-31, miR-122, miR-221, miR-222 were significantly up-regulated in HCC tissues, whereas miR-145, miR-146a, miR-200c, and miR-223 were found to be down-regulated [15]. [score:7]
However, authors concluded that high level of miR-21, miR-31, miR-122, and miR-221 expression was correlated with cirrhosis but only miR-21 and miR-221 were associated with tumor stage. [score:3]
[1 to 20 of 2 sentences]
28
[+] score: 9
mIR-122 may affect type I IFN expression in tissues of immune origin by blocking suppression by cytokine signaling [37]. [score:4]
Importantly, mir-122 participates in natural killer (NK) cell activation by increasing expression of CD69, an activation receptor for NK cells, as well as increasing secretion of IFNγ [38]. [score:3]
Although mIR-122 has been reported to be a liver-specific miRNA; its presence in spleen could be due to species differences or the migration of leukocytes between organs. [score:1]
Most have not been associated with virus infection; however three, miR-122, miR-324 and let-7, have been identified in studies of host responses to viruses [34– 36]. [score:1]
[1 to 20 of 4 sentences]
29
[+] score: 9
AST and ALT were increased when animals were given liver or skeletal muscle toxicants, demonstrating that miR-122 was indicative of liver injury only and not muscle injury, thus displaying an advantage in specificity over ALT and AST. [score:1]
Interestingly, liver enriched miR-122-5p was increased in a dose and time dependent manner while AST and ALT were increased in the 45ug/kg treated dogs with no observed histopatholgic correlate. [score:1]
In a further study miR-122, HMGB1, Cytokeratin 18 and GLDH were able to predict patients who would develop liver failure as a result of acetaminophen overdose even when ALT remained in the normal range [25]. [score:1]
Clinical chemistry parameters including amylase and lipase (markers of pancreas injury), miR-122-5p (liver enriched), miR-133a-3p (muscle enriched), 148a-3p (pancreas enriched), 208a-3p (heart enriched) and pancreas miRNAs conserved between rat and dog (Table  2) were examined for changes in the serum. [score:1]
The rat caerulein study did not generate similar miR-122 increases. [score:1]
It is possible that, due to species differences in injury and physical proximity, pancreatic damage induced by caerulein in dogs caused some perturbation of the membranes of hepatocytes resulting in AST, ALT and miR-122-5p increases in the serum while not producing similar results in the rat. [score:1]
Additionally, miR-122 and liver enriched miR-192 were increased in the serum of patients who had acetaminophen induced hepatotoxicity demonstrating the potential for these miRNAs to be used as both preclinical and clinical biomarkers for liver injury [24]. [score:1]
Interestingly, liver enriched miR-122-5p was increased in a dose and time dependent manner while AST and ALT were increased in the 45 μg/kg treated dogs while no histopatholgic correlate was observed (data not shown). [score:1]
Mice treated with acetaminophen displayed increases of miR-122 in the serum 2 h before an increase of AST/ALT [23]. [score:1]
[1 to 20 of 9 sentences]
30
[+] score: 9
Lee et al. [33] showed that cisplatin treatment mostly downregulated miR-122, whereas it upregulated miR-34a expression using microarray analyses in mouse kidneys injured by treatment with cisplatin, indicating that both miR-34a and miR-122 are involved in the molecular biological mechanism of cisplatin -induced nephrotoxicity. [score:9]
[1 to 20 of 1 sentences]
31
[+] score: 8
For instance, miR-223 was strongly up-regulated in hepatic IRI, whereas miR-122 and miR-146a were markedly down-regulated [11– 13]. [score:7]
Several studies have suggested the important roles of miRNAs in I/R injury, such as miR-122, miR-124, miR-146a, miR-223, miR-370 [11– 15]. [score:1]
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32
[+] score: 8
Researchers have observed altered expression of miR-33a/miR-33b [*] and miR-122 in liver samples, which have been designated possible contributors to hepatic lipid metabolism in patients with NAFLD [16]. [score:3]
Auguet, T. et al. miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease. [score:3]
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]
[1 to 20 of 3 sentences]
33
[+] score: 7
By using in vivo administration of siRNA targeting 2 different hepatocyte-expressed genes in the mouse and hamster liver, they did not observe any effect on endogenous miRNAs that are known to be expressed in hepatocytes (miR122, miR16, let-7a) and concluded that gene silencing using siRNA can be achieved without alteration of cellular miRNA biogenesis and function [25]. [score:7]
[1 to 20 of 1 sentences]
34
[+] score: 7
This demonstrated 63 microRNAs were significantly upregulated and 3 significantly downregulated (miR-122, miR-296-5p and miR-503) (Fig. 1A & 1B). [score:7]
[1 to 20 of 1 sentences]
35
[+] score: 7
Further microRNA-gene networks indicated that the key microRNAs were Homo sapiens (hsa)-miR-570, hsa-miR-122, hsa-miR-34b, hsa-miR-29c, hsa-miR-922 and hsa-miR-185, which negatively regulated ~79 downstream target genes to modulate hepatocyte immune response, inflammatory response and glutathione metabolism (10). [score:4]
Chronic ethanol feeding was observed to alter the expression levels of several miRNAs during liver regeneration, including miR-34a, miR-103, miR-107, miR-122 (11) and miR-21 (12). [score:3]
[1 to 20 of 2 sentences]
36
[+] score: 6
Other miRNAs from this paper: rno-mir-33
For example, miR-122 plays a critical role in the inhibiting expression of mRNA that encodes proteins involved in fatty acid oxidation and cholesterol degradation [35]. [score:5]
In addition, NASH is associated with drastic changes in the levels of various hepatic microRNAs including miR-122 [36]. [score:1]
[1 to 20 of 2 sentences]
37
[+] score: 5
We did not observe any alterations in the expression of mir122 in the liver of transgenic Tet29 rats after long term shRNA induction by low dose DOX treatment (Figure 4A). [score:3]
Furthermore, mir122 processing was unchanged in DOX treated rats in comparison to controls. [score:1]
The probe for mir122 was generated by annealing oligonucleotides rmir122a: 5′- GTA ATA CGA CTC ACT ATA GGG AAA CAC CAT TGT CAC ACT CCA GAG CTC TGC TAA GG -3′ and rmir122b: 5′-CCT TAG CAG AGC TCT GGA GTG TGA CAA TGG TGT TTC CCT ATA GTG AGT CGT ATT AC -3′, containing a T7 promoter. [score:1]
[1 to 20 of 3 sentences]
38
[+] score: 5
For example, miR-122 and its host gene regulate cholesterol and lipid metabolism in liver [35]; miR-143 and its target gene, HK2, regulates aerobic glycolysis in tumor cells [36- 39]. [score:5]
[1 to 20 of 1 sentences]
39
[+] score: 5
Xu Y MicroRNA-122 confers sorafenib resistance to hepatocellular carcinoma cells by targeting IGF-1R to regulate RAS/RAF/ERK signaling pathwaysCancer Lett. [score:3]
Bai S MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenibJ. [score:2]
[1 to 20 of 2 sentences]
40
[+] score: 5
Other miRNAs from this paper: rno-mir-328a, rno-mir-27b
Quantitative Real-Time RT-PCR Analyses of miR-27b, miR-122, and miR-328a Expression. [score:3]
miR-27b, miR-122, and miR328a have been recently reported to be associated with the regulation of CYP enzymes [48– 50]. [score:2]
[1 to 20 of 2 sentences]
41
[+] score: 5
Other miRNAs from this paper: rno-mir-330, rno-mir-343
However, it is of note that Stanzione et al. recently reported that decrease in expression of brain miR-122, which exists on the Chr-18 QTL region, is an early marker of cerebral stroke in SHRSP under salt-loading [21]. [score:3]
Stanzione R A decrease of brain MicroRNA-122 level is an early marker of cerebrovascular disease in the stroke-prone spontaneously hypertensive ratOxid. [score:2]
[1 to 20 of 2 sentences]
42
[+] score: 4
Conversely, silencing of endogenous miR-122 in mice caused the preferential up-regulation of transcripts containing miR-122 binding sites [9]. [score:4]
[1 to 20 of 1 sentences]
43
[+] score: 4
Interestingly, miRNAs have been shown to play a role in modulating the expression of a number of key players in iron homeostatic regulation, including hepcidin (miR-122; [47]), DMT1 (Let-7d; [48]) and FPN (miR-485-3p; [30]). [score:4]
[1 to 20 of 1 sentences]
44
[+] score: 4
Other specifically expressed miRNAs that we verified are mir-208, which is known to be restricted to the heart [47] and mir-122, the most prominent miRNA in liver [48]. [score:3]
For instance, reads from the rno-mir-122-5p contribute to more than 20% of all reads from known miRNAs from liver. [score:1]
[1 to 20 of 2 sentences]
45
[+] score: 4
Based on a miRNA silencing study of miR-122 in mice, the inconsistency between in silico prediction analysis and in vivo data on miRNA targets is large [6]. [score:3]
This together with reports on multiple transcript variants of miR-122 [5] might explain the variation in miR-122a levels in livers from rats without food restriction. [score:1]
[1 to 20 of 2 sentences]
46
[+] score: 4
Plasma miRNA-122. [score:1]
Furthermore, there was no significant difference between miRNA-122 copy number in plasma samples between groups (Fig 6D). [score:1]
Plasma chemistry and miRNA-122 copy number. [score:1]
Unpaired t-tests and statistical analyses were performed using GraphPad Prism 6.00 (La Jolla, CA) on maximum RE values, plasma chemistry and miRNA122 copy number. [score:1]
[1 to 20 of 4 sentences]
47
[+] score: 4
Indeed, miR-122 was highly expressed in the liver and bile duct in our study. [score:3]
miR-122 is a well-known liver-specific miRNA [11], and a number of studies have reported the usefulness of miR-122 as a biomarker for liver injury [28, 29]. [score:1]
[1 to 20 of 2 sentences]
48
[+] score: 4
miR-122 in valves (J–K) and ventricle (L). [score:1]
The ISH signal for miR-1 was more intense in the myocardium than in the valves (Figure 5G, H and I), and staining for miR-204 and 125b-5p was more intense in the valves than in the rest of the heart (Figure 5A to F), ISH of the liver-enriched miR-122 was performed and used as a negative control (Figure 5J, K and L). [score:1]
0052442.g005 Figure 5Localization of miR-204, miR-125b-5p, miR-1 and miR-122 in rat heart by in situ hybridization. [score:1]
Localization of miR-204, miR-125b-5p, miR-1 and miR-122 in rat heart by in situ hybridization. [score:1]
[1 to 20 of 4 sentences]
49
[+] score: 4
A recent study showed that the serum levels of miR-122-5p, miR-125b-5p and miR-21-5p were significantly upregulated in patients with bone fracture in comparison with healthy controls [21], implying the potential values of these miRNAs as biomarkers for bone fracture. [score:4]
[1 to 20 of 1 sentences]
50
[+] score: 3
Other miRNAs from this paper: hsa-mir-122
The 5’ untranslated region sequences of these hepaciviruses contain two miR-122 seed sites (CACUCC), which were located 51 nucleotides from each other, as consistent with the suspected hepatotropism of the viruses. [score:3]
[1 to 20 of 1 sentences]
51
[+] score: 3
Other miRNAs from this paper: hsa-mir-122
Another reason for the expression of this gene may be related to the microRNAs, their function in lipid homeostasis and interestingly where the role of especially GLD2 in the 3’-end adenylation of miR-122 was found [36, 37]. [score:3]
[1 to 20 of 1 sentences]
52
[+] score: 3
A decrease of brain microRNA-122 level is an early marker of cerebrovascular disease in the stroke-prone spontaneously hypertensive rat. [score:3]
[1 to 20 of 1 sentences]
53
[+] score: 3
Although targeting the liver-specific miR-122 by using an antisense -based approach is not related to IPF, this method is currently under human trials for the treatment of the hepatitis C virus. [score:3]
[1 to 20 of 1 sentences]
54
[+] score: 3
Specifically, some studies have focused on the roles of miRNAs in the protective effects of fish oil or omega-3 PUFAs against metabolic syndrome and found that the intake of fish oil or DHA/EPA can modify the expression of miR-30b and miR-378 [49], miR-33a and miR-122 [50], miR-107 [51], miR-192, and miR-30c [52]. [score:3]
[1 to 20 of 1 sentences]
55
[+] score: 3
The expression of miR-122, miR-93, miR-103, miR-107, miR-206, miR-143, miR-24, and miR-106b were reduced upon treatment with Tg and Tm in H9c2 cells. [score:3]
[1 to 20 of 1 sentences]
56
[+] score: 3
Many of the best-studied miRNAs contained TFBS (e. g., mir-200a, b, c; mir-125a; let-7b), including those that have wide tissue expression patterns (e. g. mir-16-2) and others enriched in specific organs such as brain (mir-124-1,2) or liver (mir-122) [7]. [score:3]
[1 to 20 of 1 sentences]
57
[+] score: 2
miR-122 has been the most thoroughly studied miRNA with regard to liver pathophysiology. [score:1]
miR-122 is highly abundant in the human liver and is essential for HCV replication [6, 7]. [score:1]
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58
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Valdmanis PN RNA interference -induced hepatotoxicity results from loss of the first synthesized isoform of microRNA-122 in miceNat. [score:1]
Indeed, previous reports suggested that the major driver of small hairpin RNA hepatotoxicity in mice is perturbation of the most abundant hepatocyte-specific miRNA, miR-122 18, 19. [score:1]
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Comparison of whey and serum qPCR analyses using the same volumes of samples showed that only miR-192, miR-150, and miR-223 (apart from the tissue-specific miRNAs miR-451 and miR-122) were detected at higher levels in serum than in whey. [score:1]
Tissue-specific miRNAs (miR-451 and miR-122) were only detected in whey at very low levels by qPCR (Fig. 6D). [score:1]
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Several candidate therapeutic miRNAs have progressed into clinical and preclinical development; for example, antisense miR-122 is being developed as a treatment for hepatitis C virus, miR-208/499 for chronic heart failure, miR-195 for myocardial infarction and miR-34 and let-7 for cancer 10, 11. [score:2]
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And Mir375 is one of a number of involved in insulin synthesis and secretion (for instance Mir9 and Mir29a/b/c), insulin sensitivity in target tissue (Mir143 and Mir29) or glucose and lipid metabolism (Mir103/107 and Mir122) and thus, having potential roles in diabetes [see for instance, [52], [53]. [score:2]
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Janssen et al. reported phase 2a clinical trial results showing that Miravirsen, which sequesters miR-122, dose -dependently and sustainably decreased HCV RNA levels in patients with chronic HCV infection [44]. [score:1]
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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-17, hsa-mir-18a, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-26a-1, hsa-mir-99a, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-106a, hsa-mir-107, mmu-let-7g, mmu-let-7i, mmu-mir-99a, mmu-mir-101a, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-126a, mmu-mir-127, mmu-mir-145a, mmu-mir-146a, mmu-mir-129-1, mmu-mir-206, hsa-mir-129-1, hsa-mir-148a, mmu-mir-122, mmu-mir-143, hsa-mir-139, hsa-mir-221, hsa-mir-222, hsa-mir-223, mmu-let-7d, mmu-mir-106a, hsa-let-7g, hsa-let-7i, hsa-mir-122, hsa-mir-125b-1, hsa-mir-143, hsa-mir-145, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-129-2, hsa-mir-146a, hsa-mir-206, mmu-mir-148a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-18a, mmu-mir-20a, mmu-mir-21a, mmu-mir-22, mmu-mir-26a-1, mmu-mir-129-2, mmu-mir-103-1, mmu-mir-103-2, rno-let-7d, rno-mir-335, rno-mir-129-2, rno-mir-20a, mmu-mir-107, mmu-mir-17, mmu-mir-139, mmu-mir-223, mmu-mir-26a-2, mmu-mir-221, mmu-mir-222, mmu-mir-125b-1, hsa-mir-26a-2, hsa-mir-335, mmu-mir-335, 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-17-1, rno-mir-18a, rno-mir-21, rno-mir-22, rno-mir-26a, rno-mir-99a, rno-mir-101a, rno-mir-103-2, rno-mir-103-1, rno-mir-107, rno-mir-125a, rno-mir-125b-1, rno-mir-125b-2, rno-mir-126a, rno-mir-127, rno-mir-129-1, rno-mir-139, rno-mir-143, rno-mir-145, rno-mir-146a, rno-mir-206, rno-mir-221, rno-mir-222, rno-mir-223, hsa-mir-196b, mmu-mir-196b, rno-mir-196b-1, hsa-mir-20b, hsa-mir-451a, mmu-mir-451a, rno-mir-451, hsa-mir-486-1, hsa-mir-499a, mmu-mir-486a, mmu-mir-20b, rno-mir-20b, rno-mir-499, mmu-mir-499, mmu-mir-708, hsa-mir-708, rno-mir-17-2, rno-mir-708, hsa-mir-103b-1, hsa-mir-103b-2, mmu-mir-486b, rno-mir-126b, hsa-mir-451b, hsa-mir-499b, mmu-mir-145b, mmu-mir-21b, mmu-let-7j, mmu-mir-130c, mmu-mir-21c, mmu-mir-451b, mmu-let-7k, hsa-mir-486-2, mmu-mir-129b, mmu-mir-126b, rno-let-7g, rno-mir-148a, rno-mir-196b-2, rno-mir-486
For example, miR-122 was decreased by E [2] in skin, but increased in gills, intestine. [score:1]
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Some miRNAs, including miR-1, miR-145, miR-122, miR-221, and miR-222, have been linked to vascular endothelial dysfunction [12]. [score:1]
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Circulating liver-specific miR-122 as a novel potential biomarker for diagnosis of cholestatic liver injury. [score:1]
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Many miRNAs, such as miR-122 (Santaris Pharma, Denmark) and miR-34 (Mirna Therapeutics, USA), need to be studied clinically 53. [score:1]
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Hepatic and serum levels of miR-122 after chronic HCV -induced fibrosis. [score:1]
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Interestingly, the miRNA families that had common members, including mir-122 (miRBase family accession # MIPF0000095) and mir-8 (miRBase family accession # MIPF0000019) had very similar fold changes and p-values within the same comparisons. [score:1]
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Other miRNAs from this paper: rno-mir-34a, rno-mir-200a, rno-mir-200b
miRNA results were examined in more detail by qRT-PCR for miR-34a and three other miRNAs (miR-122 and miR-200a/b) that were perturbed by 30 mg/kg bw/day furan treatment over 3 months in male Sprague- Dawley (SD) rats in another study (Chen et al. 2012). [score:1]
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We were able to detect miR-10a, -29a, -98, -99a, -124a, -134, and -183, but not miR-122, miR-143, and miR-153 even after 50 cycles of PCR, although they were previously reported from TG via Northern analysis [11]. [score:1]
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Baselga-Escudero L. Pascual-Serrano A. Ribas-Latre A. Casanova E. Salvadó M. J. Arola L. Arola-Arnal A. Bladé C. Long-term supplementation with a low dose of proanthocyanidins normalized liver miR-33a and miR-122 levels in high-fat diet -induced obese ratsNutr. [score:1]
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