J Cancer 2020; 11(6):1424-1435. doi:10.7150/jca.32886

Research Paper

The microRNA212 regulated PEA15 promotes ovarian cancer progression by inhibiting of apoptosis

Yonghong Luo1, Chuanchuan Fang2, Lan Jin1, Huafeng Ding1, Yuanyuan Lyu1✉, Guantai Ni1✉

1. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wannan Medical College, Wuhu, AnHui, 241001, P.R. China
2. Wannan Medical College, Wuhu, AnHui, 241001, P.R. China

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Citation:
Luo Y, Fang C, Jin L, Ding H, Lyu Y, Ni G. The microRNA212 regulated PEA15 promotes ovarian cancer progression by inhibiting of apoptosis. J Cancer 2020; 11(6):1424-1435. doi:10.7150/jca.32886. Available from https://www.jcancer.org/v11p1424.htm

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Abstract

PEA15 (Proliferation And Apoptosis Adaptor) is a 15kDa multifunctional phosphoprotein involved in various essential biological processes such as proliferation and apoptosis of cancer cells. Previous studies have demonstrated that PEA15 can promote the progression of many malignancies. In the present study, the expression of PEA15 in ovarian cancer and normal tissues analyzed in several databases and PEA15 was found to be significantly up-regulated in OC tissues compared to normal tissues. Immunochemical assays performed using 171 OC tissue specimens proved that the expression of PEA15 was remarkably positively correlated with the FIGO stage and associated with histologic subgroups of ovarian cancer. IHC assay for the two phosphorylation sites of PEA15 S116 and S104 was also performed. PEA15 high expression predicted a poor prognosis in OC patients analysed from K-M plot dataset. In addition, we proved knockdown of PEA15 inhibits OC cell proliferation and induces cell apoptosis by Bcl2 downregulation and Bax and cleaved Caspase-3 upregulation. Overexpression of PEA15 promotes the proliferative capacity of OC cells. Moreover, this study first discovered PEA15 expression in OC can be negatively regulated by microRNA212. Overexpression of miR-212 in ovarian cancer cells could cause downregulated the expression of PEA15 expression. Overexpression of miR-212 was found to exerted similar effects on the proliferation, and apoptosis of the ovarian cancer cells as that of PEA15 suppression. Additionally, overexpression of PEA15could at least partially abolished the effects of miR-212 on the proliferation, and apoptosis of ovarian cancer cells. In conclusion, our findings revealed PEA15 appears as a novel predictive biomarker, thus providing a valuable therapeutic target in OC treatment strategy.

Keywords: PEA15, miR212, Proliferation, Apoptosis, OC