MicroRNA-139 inhibits hepatocellular carcinoma cell growth through down-regulating karyopherin alpha 2

• Published in: Journal of experimental & clinical cancer research Vol. 38; no. 1; pp. 182 - 15
• Main Authors: Zan, Ying, Wang, Baofeng, Liang, Liang, Deng, Yujiao, Tian, Tian, Dai, Zhijun, Dong, Lei
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.05.2019; BioMed Central; BMC
• Subjects: Analysis; Apoptosis; Binding sites; Biomarkers; Breast cancer; Cancer; Cancer therapies; Carcinoma; Care and treatment; Cell cycle; Cell growth; Cells (Biology); Colony formation; Colorectal cancer; Development and progression; Epithelial-to-mesenchymal transition; Gastric cancer; Gene expression; Genetic aspects; Growth; Hepatocellular carcinoma; Kinases; Liver cancer; Medical prognosis; Metastasis; MicroRNA; MicroRNAs; Migration and invasion; Molecular biology; Patients; Phenotypes; Physiological aspects; Proteins; Roles; Statistics; Stem cells; Studies; Surgery; Survival; China; United States > US; Migration and invasion; Colony formation; Survival; Epithelial-to-mesenchymal transition
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-019-1175-2

MicroRNA-139-5p (miR-139) has been shown to play important roles in hepatocellular carcinoma (HCC) development. However, the exact mechanism of miR-139 in HCC remains largely unknown. We investigated the function in human cell lines and patient tissue samples by experimental techniques in molecular biology including Co-IP assay, cell viability assay, quantitative real-time-PCR, et al. In addition, datasets were used to verify the results by database analysis. Statistical analysis was performed by using the GraphPad Prism 6 (GraphPad Software Inc., USA). A P value < 0.05 was defined as statistically significant. In this study, we found that miR-139 was significantly down-regulated in HCC. MiR-139 level was negatively associated with the stage of HCC, and HCC patients with higher miR-139 level had longer overall survival (OS) than these having lower miR-139 expression. Overexpression of miR-139 led to reduced cell viability, elevated apoptosis, and decreased colony forming, migratory and invasive capacities in HCC cells, while down-regulation of miR-139 led to opposite phenotypes. MiR-139 also inhibited HCC growth in a xenograft mouse model. We identified karyopherin alpha 2 (KPNA2) as a direct target of miR-139. KPNA2 is up-regulated in HCC and higher KPNA2 level is associated with poor patient prognosis. Silencing of KPNA2 expression led to similar phenotypic changes as miR-139 overexpression. Restoration of KPNA2 attenuated the suppressive effects of miR-139 overexpression on cell viability, apoptosis, colony formation, migration and invasion. In addition, miR-139 overexpression and KPNA2 depletion led to decreased nucleus level of POU class 5 homeobox 1 (POU5F1) and c-myc, two well-known pro-oncogenes. In together, these data revealed the essential roles of the miR-139/KPNA2 axis in HCC.