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

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

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
Source :
Journal of Hematology & Oncology, Vol 11, Iss 1, Pp 1-12 (2018)
Publication Year :
2018
Publisher :
BMC, 2018.

Abstract

Abstract 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-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a. Conclusions 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.

Details

Language :
English
ISSN :
17568722
Volume :
11
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Hematology & Oncology
Publication Type :
Academic Journal
Accession number :
edsdoj.b5ff33fdd4f47ae85573d269ef5adff
Document Type :
article
Full Text :
https://doi.org/10.1186/s13045-018-0555-y