Zhang Qingmei, Chen Xiufeng, Zhang Xuan, Zhan Jingfen, Chen Jie
FuJian University of Traditional Chinese Medicine, Fuzhou 350122, China.
Department of Obstetrics and Gynecology, Longyan Hospital of Traditional Chinese Medicine, Longyan 364000, China.
Biosci Rep. 2016 Feb 19;36(1):e00298. doi: 10.1042/BSR20150258. Print 2016.
Transmembrane protein 14A (TMEM14A) is a member of TMEMs. Alterations in TMEMs expression have been identified in several types of cancer, but the expression and function of TMEM14A in ovarian cancer is still unclear. Here, analysis on the expression data of the Cancer Genome Atlas (TCGA) ovarian serous cystadenocarcinoma (OV) dataset demonstrated the overexpression of TMEM14A in ovarian cancer tissues compared with normal tissues, which was consistent with our real-time PCR analysis on ovarian cancer and normal tissues collected from 30 patients. In addition, TMEM14A knockdown in two ovarian cancer cell lines, A2780 and HO-8910, reduced cell proliferation, causes cell cycle arrest and suppressed cell invasion. Moreover, silencing of TMEM14A notably repressed G1/S cell cycle transition and cell invasion via down-regulating the expression of cell cycle related proteins (Cyclin D1, Cyclin E and PCNA) and metastasis-related proteins (MMP-2 and MMP-9), respectively. TMEM14A knockdown significantly reduced the phosphorylation status of Smad2 and Smad3, downstream effectors of TGF-β signalling. In summary, these results indicate that TMEM14A has a pro-tumorigenic effect in ovarian cancer cells, suggesting an important role of this protein in ovarian cancer oncogenesis and metastasis.
跨膜蛋白14A（TMEM14A）是跨膜蛋白家族（TMEMs）的成员之一。在多种癌症类型中已发现TMEMs表达存在改变，但TMEM14A在卵巢癌中的表达及功能仍不清楚。在此，对癌症基因组图谱（TCGA）卵巢浆液性囊腺癌（OV）数据集的表达数据进行分析表明，与正常组织相比，TMEM14A在卵巢癌组织中过表达，这与我们对30例患者收集的卵巢癌组织和正常组织进行的实时PCR分析结果一致。此外，在两种卵巢癌细胞系A2780和HO - 8910中敲低TMEM14A可降低细胞增殖、导致细胞周期停滞并抑制细胞侵袭。而且，沉默TMEM14A分别通过下调细胞周期相关蛋白（细胞周期蛋白D1、细胞周期蛋白E和增殖细胞核抗原）和转移相关蛋白（基质金属蛋白酶 - 2和基质金属蛋白酶 - 9）的表达，显著抑制G1/S期细胞周期转换和细胞侵袭。TMEM14A敲低显著降低了TGF - β信号通路下游效应分子Smad2和Smad3的磷酸化状态。总之，这些结果表明TMEM14A在卵巢癌细胞中具有促肿瘤作用，提示该蛋白在卵巢癌发生和转移中具有重要作用。
