NCAPG2 overexpression promotes hepatocellular carcinoma proliferation and metastasis through activating the STAT3 and NF-κB/miR-188-3p pathways

NCAPG2过表达通过激活STAT3和NF-κB / miR-188-3p通路促进肝细胞癌增殖和转移

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作者:Fanzheng Meng, Shugeng Zhang, Ruipeng Song, Yao Liu, Jiabei Wang, Yingjian Liang, Jizhou Wang, Jihua Han, Xuan Song, Zhaoyang Lu, Guangchao Yang, Shangha Pan, Xianying Li, Yufeng Liu, Fang Zhou, Yan Wang, Yifeng Cui, Bo Zhang, Kun Ma, Congyi Zhang, Yufei Sun, Mengyang Xin, Lianxin Liu

Background

Hepatocellular carcinoma (HCC) is a highly fatal malignant cancer worldwide. Elucidating the underlying molecular mechanism of HCC progression is critical for the identification of new therapeutic targets for HCC. This study aimed to determine the role of Non-SMC condensin II complex subunit G2 (NCAPG2) in HCC proliferation and metastasis.

Methods

We detected NCAPG2 expression in tissues using immunohistochemistry, western blotting and real-time PCR. The effects of NCAPG2 on cell proliferation and metastasis were evaluated both in vitro and in vivo. Immunocytochemistry, enzyme linked immunosorbent assay, co-immunoprecipitation and luciferase reporter assay were performed to uncover the underlying mechanisms. Findings: We found that NCAPG2 is frequently upregulated in HCC tumour tissues and predicts a poor prognosis. NCAPG2 overexpression promotes HCC proliferation, migration, and invasion through activating STAT3 and NF-κB signalling pathways. Moreover, NCAPG2 is a direct target of miR-188-3p. We demonstrated the existence of a positive feedback loop between NCAPG2 and p-STAT3 and a negative feedback loop between NCAPG2 and miR-188-3p. Interpretation: Our study indicates that NCAPG2 overexpression could drive HCC proliferation and metastasis through activation of the STAT3 and NF-κB/miR-188-3p pathways. These findings may contribute to the identification of novel biomarkers and therapeutic targets for HCC. FUND: National Key Program for Science and Technology Research and Development (Grant No. 2016YFC0905902); the National Natural Scientific Foundation of China (Nos. 81772588, 81602058, 81773194); University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (Grant No. UNPYSCT-2016200); the Innovative Research Program for Graduate of Harbin Medical University (Grant Nos. YJSCX2017-38HYD, YJSCX2016-18HYD).

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