Ontology highlight
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.
SUBMITTER: Cao MQ
PROVIDER: S-EPMC5782375 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
Cao Man-Qing MQ You A-Bin AB Zhu Xiao-Dong XD Zhang Wei W Zhang Yuan-Yuan YY Zhang Shi-Zhe SZ Zhang Ke-Wei KW Cai Hao H Shi Wen-Kai WK Li Xiao-Long XL Li Kang-Shuai KS Gao Dong-Mei DM Ma De-Ning DN Ye Bo-Gen BG Wang Cheng-Hao CH Qin Cheng-Dong CD Sun Hui-Chuan HC Zhang Ti T Tang Zhao-You ZY
Journal of hematology & oncology 20180124 1
<h4>Background</h4>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.<h4>Methods</h4>Real-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression o ...[more]