MiR-706 inhibits the oxidative stress-induced activation of PKC?/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 ?-SMA. Subsequent studies revealed that miR-706 directly inhibits PKC? 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 ?-SMA, PKC?, 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 PKC?/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.

SUBMITTER: Yin R 

PROVIDER: S-EPMC5120320 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature