TOP2A promotes proliferation and metastasis of hepatocellular carcinoma regulated by miR-144-3p.
TOP2A promotes proliferation and metastasis of hepatocellular carcinoma regulated by miR-144-3p.
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DOI：
10.7150/jca.64017
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发表时间：
2022
影响因子：
3.9
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Wang T;Lu J;Wang R;Cao W;Xu J
拓扑异构酶IIα(TOP2A)是一种重要的核蛋白，广泛存在于多种肿瘤中。TOP2A在肝细胞癌中是否发挥重要作用尚不清楚。通过生物信息学分析和临床标本验证，我们发现TOP2A在肝细胞癌中高表达，且与预后不良有关。TOP2A基因的敲除和过表达分别在体内外抑制或促进肝癌细胞的增殖、转移和侵袭。机制上，TOP2A通过抑制CHK1的磷酸化，激活细胞周期从G2期进入M期，促进上皮向间充质转化(EMT)。我们进一步证实TOP2A是miR-144-3p的直接靶点，其过表达可以部分逆转TOP2A在肝癌细胞中的作用。我们的研究结果表明，TOP2A通过促进肝癌的增殖、迁移、侵袭和EMT过程发挥作用，可作为治疗肝癌的潜在靶点。
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.