J Cancer 2022; 13(2):589-601. doi:10.7150/jca.64017 This issue

Research Paper

TOP2A promotes proliferation and metastasis of hepatocellular carcinoma regulated by miR-144-3p

Tao Wang1,2,*, Jing Lu1,*, Rangrang Wang1,*, Wanyue Cao1, Junming Xu1✉

1. Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China.
2. Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
* These authors have contributed equally to this work.

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Wang T, Lu J, Wang R, Cao W, Xu J. TOP2A promotes proliferation and metastasis of hepatocellular carcinoma regulated by miR-144-3p. J Cancer 2022; 13(2):589-601. doi:10.7150/jca.64017. Available from https://www.jcancer.org/v13p0589.htm

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Graphic abstract

Topoisomerase II alpha (TOP2A) is an important nuclear protein which is found in various types of cancers. Whether TOP2A plays an important role in hepatocellular carcinoma (HCC) remains unclear. Through bioinformatic analysis and clinical specimen verification, we found that TOP2A is highly expressed in HCC and is associated with poor prognosis. Knockdown and overexpression of TOP2A can respectively inhibit or promote proliferation, metastasis and invasion of HCC cells in vitro and in vivo. Mechanismly, TOP2A activates cell cycle progression from G2 to M phase by inhibiting the phosphorylation of CHK1 and promotes Epithelial-to-mesenchymal transition (EMT) process. We further confirmed that TOP2A is a direct target of miR-144-3p whose overexpressing can partially reverse the effect of TOP2A in HCC cells. Our data suggested that TOP2A functions by promoting the proliferation, migration, invasion and EMT process of HCC and can be considered as a potential target for the treatment of HCC.

Keywords: TOP2A, miR-144-3p, cell cycle, EMT, Hepatocellular carcinoma