Int J Med Sci 2020; 17(15):2387-2395. doi:10.7150/ijms.48615

Research Paper

CHD1L promotes EOC cell invasiveness and metastasis via the regulation of METAP2

Wei-Peng He1*, Yun-Yun Guo1*, Gui-Ping Yang1*, Hui-Ling Lai1, Ting-Ting Sun1, Zu -Wei Zhang1, Ling-Long Ouyang1, Yu Zheng1, Li-Ming Tian1, Xiao-Hui Li1, Ze-Shan You1, Dan Xie2✉, Guo-Fen Yang1✉

1. Department of Gynecology, the First Affiliated Hospital, Sun Yat-Sen University, No. 58, Zhongshan Road II, 510080 Guangzhou, China.
2. State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, 510060 Guangzhou, China.
*These authors contributed equally to this work.

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Citation:
He WP, Guo YY, Yang GP, Lai HL, Sun TT, Zhang ZW, Ouyang LL, Zheng Y, Tian LM, Li XH, You ZS, Xie D, Yang GF. CHD1L promotes EOC cell invasiveness and metastasis via the regulation of METAP2. Int J Med Sci 2020; 17(15):2387-2395. doi:10.7150/ijms.48615. Available from http://www.medsci.org/v17p2387.htm

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Abstract

Chromodomain helicase DNA binding protein 1-like (CHD1L) gene has been proposed to play an oncogenic role in human hepatocellular carcinoma. Previously we reported that CHD1L overexpression is significantly associated with the metastasis proceeding of epithelial ovarian cancer (EOC), and may predict a poor prognosis in EOC patients. However, the potential oncogenic mechanisms by which CHD1L acts in EOC remain unclear. To elucidate the oncogenic function of CHD1L, we carried out a series of in vitro assays, with effects of CHD1L ectogenic overexpression and silencing being determined in EOC cell lines (HO8910, A2780 and ES2). Real-time PCR and Western blotting analyses were used to identify potential downstream targets of CHD1L in the process of EOC invasion and metastasis. In ovarian carcinoma HO8910 cell lines, ectopic overexpression of CHD1L substantially induced the invasive and metastasis ability of the cancer cells in vitro. In contrast, knockdown of CHD1L using shRNA inhibited cell invasion in vitro in ovarian carcinoma A2780 and ES2 cell lines. We also demonstrated that methionyl aminopeptidase 2 (METAP2) was a downstream target of CHD1L in EOC, and we found a significant, positive correlation between the expression of CHD1L and METAP2 in EOC tissues (P<0.05). Our findings indicate that CHD1L plays a potential role in the inducement of EOC cancer cell invasion and/or metastasis via the regulation of METAP2 expression and suggests that CHD1L inhibition may provide a potential target for therapeutic intervention in human EOC.

Keywords: Ovarian cancer, CHD1L, invasion, metastasis, METAP2