期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 103, 期 -, 页码 1632-1642出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.03.005
关键词
miR-300; FAK; PI3K/AKT; EMT; Invasion; Hepatocellular carcinoma
资金
- National Natural Science Foundation of China [81472258, 81472253]
- National Science Foundation of Guangdong Province [2014A030313063]
- Project of Guangzhou Municipal Science & Technology Planning [201607010309, 201607010164]
- Science and Technology Planning Project of Guangdong Province [2016A020215047, 2017A020215016, 2016A030303005, 2014A020212083]
Several 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, upregulation of miR-300 led to the opposite results. Ectopic overexpression of miR-300 reversed TGF-beta 1-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.
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