title: miR-706 inhibits the oxidative stress-induced activation of PKCα/TAOK1 in liver fibrogenesis.
abstract: Oxidative stress induces the activation of liver fibrogenic cells (myofibroblasts), thus promoting the expression of fibrosis-related genes, leading to hepatic fibrogenesis. MicroRNAs (miRNAs) are a new class of small RNAs ~18-25 nucleotides in length involved in post-transcriptional regulation of gene expression. Wound-healing and remodeling processes in liver fibrosis have been associated with changes in hepatic miRNA expression. However, the role of miR-706 in liver fibrogenesis is currently unknown. In the present study, we show that miR-706 is abundantly expressed in hepatocytes. Moreover, oxidative stress leads to a significant downregulation of miR-706, and the further reintroduction of miR-706 inhibits oxidative stress-induced expression of fibrosis-related markers such as α-SMA. Subsequent studies revealed that miR-706 directly inhibits PKCα and TAOK1 expression via binding to the 3'-untranslated region, preventing epithelial mesenchymal transition. In vivo studies showed that intravenous injection of miR-706 agomir successfully increases hepatic miR-706 and decreases α-SMA, PKCα, and TAOK1 protein levels in livers of carbon tetrachloride (CCl4)-treated mice. In summary, this study reveals a protective role for miR-706 by blocking the oxidative stress-induced activation of PKCα/TAOK1. Our results further identify a major implication for miR-706 in preventing hepatic fibrogenesis and suggest that miR-706 may be a suitable molecular target for anti-fibrosis therapy.
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, 10 Xi tou tiao, You An Men Wai, 100069, Beijing, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Yin
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, 10 Xi tou tiao, You An Men Wai, 100069, Beijing, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Guo
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, 10 Xi tou tiao, You An Men Wai, 100069, Beijing, China.
authors.forename: Shuxian
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, 10 Xi tou tiao, You An Men Wai, 100069, Beijing, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D018384:Oxidative Stress; D051571:Protein Kinase C-alpha / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: C000627628:MIRN706 microRNA, human; C000627627:MIRN706 microRNA, mouse; D035683:MicroRNAs; D002251:Carbon Tetrachloride; D017346:Protein Serine-Threonine Kinases; C115483:TAO1 protein kinase; D051571:Protein Kinase C-alpha