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

作者：Manqing Cao, A‐Bin You, Xiao‐Dong Zhu, Wei Zhang, Yuanyuan Zhang, Shi-Zhe Zhang, Kewei Zhang, Hao Cai, Wen-Kai Shi, Xiao‐Long Li, Kangshuai Li, Dongmei Gao, De-Ning Ma, Bo-Gen Ye, Chenghao Wang, Chengdong Qin, Hui‐Chuan Sun, Ti Zhang, Zhao–You Tang · 发表于：Journal of Hematology & Oncology · 年份：2018 · DOI：10.1186/s13045-018-0555-y · 被引用次数：241 · 研究领域：FOXO transcription factor regulation、MicroRNA in disease regulation、Circular RNAs in diseases

BACKGROUND: 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. METHODS: 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. RESULTS: 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-cat...