• Rongchang Wang, Zheng Yu, Fan Chen, Hongxu Xu, Shunli Shen, Wei Chen, Lianzhou Chen, Qiao Su, Longjuan Zhang, Jiong Bi, Wentao Zeng, Wen Li, Xiaohui Huang, and Qian Wang.
• Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan Road 2, Guangzhou, 510080, PR China.
• Biomed. Pharmacother. 2018 Jul 1; 103: 1632-1642.

AbstractSeveral microRNAs (miRNAs) have been closely correlated with the development of hepatocellular carcinoma (HCC). However, the involvement of miR-300 in the development of HCC remains unknown. This study elucidated the potential molecular mechanisms of miR-300 in the modulation of the epithelial-mesenchymal transition (EMT) and invasion of HCC. The expression levels of miR-300 in HCC cells and clinical samples were detected by quantitative real-time PCR and in situ hybridization. The in vitro function of miR-300 in HCC was evaluated using a migration/invasion assay. Quantitative real-time PCR, western blotting, immunofluorescence and immunohistochemistry were used to validate the roles of miR-300 and FAK/PI3K/AKT in EMT progression. A dual-luciferase reporter assay was performed to confirm the target gene. miR-300 was down-regulated in HCC and significantly correlated with a poor prognosis in HCC patients. The down-regulation of miR-300 increased the invasiveness of the HCC cells, and promoted the EMT in both HCC tissues and HCC cells. In contrast, up-regulation of miR-300 led to the opposite results. Ectopic overexpression of miR-300 reversed TGF-β1-induced EMT in SMMC-7721 cells, and according to a dual-luciferase reporter assay and rescue assay, miR-300 inhibits the EMT-mediated migration and invasion of HCC cells via the targeted modulation of FAK and the downstream PI3K/AKT signaling pathway. miR-300 targeting modulates FAK, and the PI3K/AKT signaling pathway inhibits the EMT and suppresses the migration and invasion of HCC cells. Thus, miR-300 represents a promising therapeutic target for HCC.Copyright © 2018 Elsevier Masson SAS. All rights reserved.

48 keywords...

hide…