miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a

• Published in: Journal of hematology and oncology 2018-01, Vol.11 (1), p.12-12, Article 12
• Main Authors: Cao, Man-Qing, You, A-Bin, Zhu, Xiao-Dong, Zhang, Wei, Zhang, Yuan-Yuan, Zhang, Shi-Zhe, Zhang, Ke-Wei, Cai, Hao, Shi, Wen-Kai, Li, Xiao-Long, Li, Kang-Shuai, Gao, Dong-Mei, Ma, De-Ning, Ye, Bo-Gen, Wang, Cheng-Hao, Qin, Cheng-Dong, Sun, Hui-Chuan, Zhang, Ti, Tang, Zhao-You
• Format: Article
• Language: English
• Subjects: Analysis; Cancer metastasis; Development and progression; FOXO3a; Genetic aspects; HCC; Hepatocellular carcinoma; MicroRNA; miR-182-5p; Physiological aspects; Wnt signaling
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-018-0555-y

High frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown. Real-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression. We showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3'-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/β-catenin signaling by inhibiting the degradation of β-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a. Consistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.