MiR-142-3p blocks TGF-β-induced activation of hepatic stellate cells through targeting TGFβRI

Yang, Xiaoxue; Dan, Xuelian; Men, Ruoting; Ma, Liping; Wen, Maoyao; Peng, Yong; Yang, Li

doi:10.1016/j.lfs.2017.08.017

Cited by 30 publications

(25 citation statements)

References 36 publications

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“…TGFBR1 has been shown in several studies to be implicated in AD pathogenesis (Caraci et al, 2012;Chen, Ke, Lu, Qiu, & Peng, 2015;Flanders, Lippa, Smith, Pollen, & Sporn, 1995;Lippa, Flanders, Kim, & Croul, 1998;Tesseur et al, 2006;Wyss-Coray et al, 2002). The regulation of TGFBR1 expression by miR-142-3p has been experimentally confirmed at mRNA and protein levels in previous studies (Talebi et al, 2017;Yang et al, 2017). Our differential expression analysis for all miR-142-3p target genes demonstrated that TGFBR1 was significantly downregulated in miR-142-3p overexpressing human iPS-derived NPCs and the top target gene upregulated in the hippocampus of miR-142 KO mice.…”

supporting

confidence: 67%

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A functional variant in the miR‐142 promoter modulating its expression and conferring risk of Alzheimer disease

Ghanbari

Munshi

et al. 2019

Human Mutation

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Noncoding RNAs have been widely recognized as essential mediators of gene regulation. However, in contrast to protein‐coding genes, much less is known about the influence of noncoding RNAs on human diseases. Here we examined the association of genetic variants located in primary microRNA sequences and long noncoding RNAs (lncRNAs) with Alzheimer disease (AD) by leveraging data from the largest genome‐wide association meta‐analysis of late‐onset AD. Variants annotated to 5 miRNAs and 10 lncRNAs (in seven distinct loci) exceeded the Bonferroni‐corrected significance threshold (p < 1.02 × 10−6). Among these, a leading variant (rs2526377:A>G) at the 17q22 locus annotated to two noncoding RNAs (MIR142 and BZRAP1‐AS) was significantly associated with a reduced risk of AD and fulfilled predefined criteria for being a functional variant. Our functional genomic analyses revealed that rs2526377 affects the promoter activity and decreases the expression of miR‐142. Moreover, differential expression analysis by RNA‐Seq in human iPSC‐derived neural progenitor cells and the hippocampus of miR‐142 knockout mice demonstrated multiple target genes of miR‐142 in the brain that are likely to be involved in the inflammatory and neurodegenerative manifestations of AD. These include TGFBR1 and PICALM, of which their derepression in the brain due to reduced expression levels of miR‐142‐3p may reduce the risk of AD.

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supporting

confidence: 67%

“…We additionally confirmed the downregulation of PICALM Table S8). Among the 12 target genes, miR-142-3p-mediated regulation of TGFBR1 and CFL2 have also been validated experimentally in the previous studies (Schwickert et al, 2015;Yang et al, 2017).…”

Section: Potential Mir-142 Target Genes Implicated In Admentioning

confidence: 81%

A functional variant in the miR‐142 promoter modulating its expression and conferring risk of Alzheimer disease

Ghanbari

Munshi

et al. 2019

Human Mutation

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“…Both let‐7g‐5p and miR‐142‐3p expression are down‐regulated in hepatocellular carcinoma (HCC) and are involved in suppressing HCC cell migration, motility, and invasion . Downregulated miR‐142‐3p has also been found in activated HSCs controlling cell viability and cell growth by targeting transforming growth factor β receptor 1 . Based on the functions that these miRNAs play in HCC and in HSCs, it is possible that their decreased expression in CFLD children may play a role in preventing fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…(46,48) Downregulated miR-142-3p has also been found in activated HSCs controlling cell viability and cell growth by targeting transforming growth factor β receptor 1. (49) Based on the functions that these miR-NAs play in HCC and in HSCs, it is possible that their decreased expression in CFLD children may play a role in preventing fibrosis. Functional studies are required to establish the origin and potential role that these differentially expressed miRNAs may play in CFLD and in the development of fibrosis.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Sequencing Identifies a Serum MicroRNA Panel, Which Combined With Aspartate Aminotransferase to Platelet Ratio Index Can Detect and Monitor Liver Disease in Pediatric Cystic Fibrosis

et al. 2018

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Cystic fibrosis (CF)-associated liver disease (CFLD) is a hepatobiliary complication of CF. Current diagnostic modalities rely on nonspecific assessments, whereas liver biopsy is the gold standard to assess severity of fibrosis. MicroRNAs (miRNAs) regulate liver disease pathogenesis and are proposed as diagnostic biomarkers. We investigated the combined use of serum miRNAs and aspartate aminotransferase (AST) to platelet ratio (APRI) to diagnose and assess CFLD severity. This was a cross-sectional cohort study of the circulatory miRNA signature of 124 children grouped by clinical, biochemical, and imaging assessments as follows: CFLD (n = 44), CF patients with no evidence of liver disease (CFnoLD; n = 40), and healthy controls (n = 40). Serum miRNAs were analyzed using miRNA sequencing (miRNA-Seq). Selected differentially expressed serum miRNA candidates were further validated by qRT-PCR and statistical analysis performed to evaluate utility to predict CFLD and fibrosis severity validated by liver biopsy, alone or in combination with APRI. Serum miR-122-5p, miR-365a-3p, and miR-34a-5p levels were elevated in CFLD compared to CFnoLD, whereas miR-142-3p and let-7g-5p were down-regulated in CFLD compared to CFnoLD. Logistic regression analysis combining miR-365a-3p, miR-142-3p, and let-7g-5p with APRI showed 21 times greater odds of accurately predicting liver disease in CF with an area under the receiver operating characteristics curve (AUROC) = 0.91 (sensitivity = 83%, specificity = 92%; P < 0.0001). Expression levels of serum miR-18a-5p were correlated with increasing hepatic fibrosis (HF) stage in CFLD (r = 0.56; P < 0.0001), showing good diagnostic accuracy for distinguishing severe (F3-F4) from mild/moderate fibrosis (F0-F2). A unit increase of miR-18a-5p showed a 7-fold increased odds of having severe fibrosis with an AUROC = 0.82 (sensitivity = 93%, specificity = 73%; P = 0.004), indicating its potential to predict fibrosis severity. Conclusion: We identified a distinct circulatory miRNA profile in pediatric CFLD with potential to accurately discriminate liver disease and fibrosis severity in children with CF.

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“…However, further mechanistic studies are required to fully elucidate the role of miR-34a-5p and miR-365a-3p in the pathogenesis of these paediatric liver diseases. HSC) controlling cell viability and cell growth by targeting TGFβ-receptor 1 (TGFβRI)(309). Based on the functions that these miRNAs play in HCC and in HSCs, it is possible that their decreased expression in CFLD children may play a role in preventing fibrosis.Functional studies are required to establish the origin and potential role that these differentially expressed miRNAs may play in CFLD and in the development of fibrosis.When APRI was combined with the proposed miRNA panel a marked improvement in discriminating CFLD from CFnoLD was observed with an AUC=0.91.…”

mentioning

confidence: 99%

Non-invasive assessment of paediatric cystic fibrosis liver disease and the role of microRNAs in disease mechanism

Calvopina¹,

Andrés²

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MiR-142-3p blocks TGF-β-induced activation of hepatic stellate cells through targeting TGFβRI

Cited by 30 publications

References 36 publications

A functional variant in the miR‐142 promoter modulating its expression and conferring risk of Alzheimer disease

A functional variant in the miR‐142 promoter modulating its expression and conferring risk of Alzheimer disease

MicroRNA Sequencing Identifies a Serum MicroRNA Panel, Which Combined With Aspartate Aminotransferase to Platelet Ratio Index Can Detect and Monitor Liver Disease in Pediatric Cystic Fibrosis

Non-invasive assessment of paediatric cystic fibrosis liver disease and the role of microRNAs in disease mechanism

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