1. microRNA-19a-3p promotes tumor metastasis and chemoresistance through the PTEN/Akt pathway in hepatocellular carcinoma
- Author
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Guangqi Song, Hong-Ying Guo, Xiaoxi Huang, Xiang-Nan Yu, Tao-Tao Liu, Ji-Min Zhu, Hai-Rong Zhu, Xuan Shi, Xuemei Jiang, Shuqiang Weng, Harry L.A. Janssen, Xizhong Shen, Ling Dong, and Enkhnaran Bilegsaikhan
- Subjects
0301 basic medicine ,Carcinoma, Hepatocellular ,Cell ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,PTEN ,Tensin ,Gene silencing ,neoplasms ,PI3K/AKT/mTOR pathway ,Pharmacology ,biology ,Liver Neoplasms ,PTEN Phosphohydrolase ,General Medicine ,medicine.disease ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Hepatocytes ,biology.protein ,Cancer research ,Ectopic expression ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
microRNA-19a-3p (miR-19a-3p) has been reported to regulate cell proliferation in hepatocellular carcinoma (HCC), but its role in HCC metastasis remains unknown. In this study, miR-19a-3p was noted to be upregulated in HCC specimens and cell lines. Aberrant expression of miR-19a-3p stimulated HCC cell metastasis, and phosphatase and tensin homolog (PTEN) was shown to be a direct target of miR-19a-3p. miR-19a-3p-mediated HCC metastasis was reversed by restoration of PTEN or could be imitated by silencing of PTEN. Modulation of miR-19a-3p also altered expression of phosphorylated Akt, a downstream mediator of PTEN. Moreover, aberrant expression of miR-19a-3p induced sorafenib resistance by regulating the PTEN/Akt pathway. In conclusion, ectopic expression of miR-19a-3p contributes to HCC metastasis and chemoresistance by modulating PTEN expression and the PTEN-dependent pathways.
- Published
- 2018