microRNA-21 mediates epithelial-mesenchymal transition of human hepatocytes via PTEN/Akt pathway

作者：Liu, Zhenyu; Wang, Jingjie; Guo, Chuanyong; Fan, Xiaoming^*

来源：Biomedicine & Pharmacotherapy, 2015, 69: 24-28.

DOI：10.1016/j.biopha.2014.10.028

• miR-21
• EMT
• PTEN/Akt

miR-21 has been shown to play fundamental role in diverse biological and pathological processes, including fibrotic diseases. In the present study, we investigated whether miR-21 regulated the fibrogenic epithelial-mesenchymal transition (EMT) in human hepatocytes QSG-7701 and explored underlying mechanisms. The results showed that treatment of QSG-7701 cells with pro-fibrogenic factor TGF-beta(1) resulted in increased expression of miR-21 and promoted fibrogenic EMT in hepatocytes. Downregulation of miR-21 expression by transfection of anti-miR-21 into QSG-7701 cells inhibited fibrogenic EMT induced by TGF-beta(1). Furthermore, overexpression of miR-21 alone also resulted in EMT-like transformation in QSG-7701 cells. TGF-beta(1) treatment resulted in decreased PTEN and increased Akt phosphorylation and anti-miR-21 abolished this effect. Overexpression of miR-21 in QSG-7701 cells also downregulated PTEN and upregulated Akt phosphralation. Inhibition of Akt signaling by specific inhibitor Akt inhibitor IV blocked TGF-beta(1) and miR-21-induced fibrogenic EMT. In summary, our results identify miR-21 as a key regulator of fibrogenic EMT in hepatocytes via PTEN/Akt pathway. Targeting miR-21 may provide a new therapeutic strategy against hepatic fibrosis.

• 出版日期2015-2
• 单位复旦大学; 同济大学