Inhibition of microRNA‐214 ameliorates hepatic fibrosis and tumor incidence in platelet‐derived growth factor C transgenic mice

• DOI: 10.1111/cas.12730
• Publication Date: 2015-06-29T10:21:22Z
• Authors: Hikari Okada; Masao Honda; Jean S. Campbell; Kai Takegoshi; Yoshio Sakai; Taro Yamashita; Takayoshi Shirasaki; Riuta Takabatake; Mikiko Nakamura; Takuji Tanaka; Shuichi Kaneko
• Keywords: Hepatic fibrosis

Differentially regulated microRNA (miRNA) are associated with hepatic fibrosis; however, their potential usefulness for blocking fibrosis has not been exploited fully. We examined the expression of miRNA in liver a transgenic mouse model which platelet-derived growth factor C (PDGF-C) is overexpressed (Pdgf-c Tg), resulting and steatosis eventual development hepatocellular carcinoma (HCC). Robust induction miR-214 correlated fibrogenesis Pdgf-c Tg mice, atherogenic high-fat diet-induced NASH patients chronic hepatitis B or C. mice were injected locked nucleic acid (LNA)-antimiR-214 via tail vein using Invivofectamine 2.0 degree tumor incidence evaluated. treated LNA-antimiR-214 showed marked reduction compared saline LNA-miR-control-injected control mice. In vitro, significantly ameliorated TGF-β1-induced pro-fibrotic gene Lx-2 cells. MiR-214 targets negative regulator EGFR signaling, Mig-6. Mimic-miR-214 decreased Mig-6 increased levels EGF-mediated p-EGFR (Y1173 Y845) p-Met (Tyr1234/1235) Huh-7 Conversely, repressed these genes. conclusion, appears to participate by modulating TGF-β signaling pathways. therapy prevention fibrosis.