Luo Yonghong, Fang Chuanchuan, Jin Lan, Ding Huafeng, Lyu Yuanyuan, Ni Guantai
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wannan Medical College, Wuhu, AnHui, 241001, P.R. China.
Wannan Medical College, Wuhu, AnHui, 241001, P.R. China.
J Cancer. 2020 Jan 13;11(6):1424-1435. doi: 10.7150/jca.32886. eCollection 2020.
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.
PEA15(增殖与凋亡衔接蛋白)是一种15千道尔顿的多功能磷蛋白,参与癌细胞增殖和凋亡等多种重要生物学过程。先前的研究表明,PEA15可促进多种恶性肿瘤的进展。在本研究中,通过多个数据库分析了PEA15在卵巢癌组织和正常组织中的表达情况,发现与正常组织相比,OC组织中PEA15显著上调。使用171例OC组织标本进行的免疫化学分析证明,PEA15的表达与FIGO分期显著正相关,且与卵巢癌的组织学亚组相关。还对PEA15的S116和S104两个磷酸化位点进行了免疫组化分析。从K-M图数据集分析可知,PEA15高表达预示OC患者预后不良。此外,我们证明敲低PEA15可抑制OC细胞增殖,并通过下调Bcl2以及上调Bax和裂解的Caspase-3诱导细胞凋亡。PEA15过表达可促进OC细胞的增殖能力。此外,本研究首次发现miR-212可负调控OC中PEA15的表达。卵巢癌细胞中miR-212过表达可导致PEA15表达下调。发现miR-212过表达对卵巢癌细胞增殖和凋亡的影响与抑制PEA15的作用相似。此外,PEA15过表达至少可部分消除miR-212对卵巢癌细胞增殖和凋亡的影响。总之,我们的研究结果表明PEA15是一种新的预测生物标志物,从而为OC治疗策略提供了有价值的治疗靶点。