Title |
miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a
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Published in |
Journal of Hematology & Oncology, January 2018
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DOI | 10.1186/s13045-018-0555-y |
Pubmed ID | |
Authors |
Man-Qing Cao, A-Bin You, Xiao-Dong Zhu, Wei Zhang, Yuan-Yuan Zhang, Shi-Zhe Zhang, Ke-wei Zhang, Hao Cai, Wen-Kai Shi, Xiao-Long Li, Kang-Shuai Li, Dong-Mei Gao, De-Ning Ma, Bo-Gen Ye, Cheng-Hao Wang, Cheng-Dong Qin, Hui-Chuan Sun, Ti Zhang, Zhao-You Tang |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 62 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 10 | 16% |
Researcher | 8 | 13% |
Student > Bachelor | 8 | 13% |
Student > Master | 7 | 11% |
Student > Doctoral Student | 2 | 3% |
Other | 4 | 6% |
Unknown | 23 | 37% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 22 | 35% |
Medicine and Dentistry | 6 | 10% |
Nursing and Health Professions | 2 | 3% |
Immunology and Microbiology | 2 | 3% |
Linguistics | 1 | 2% |
Other | 5 | 8% |
Unknown | 24 | 39% |