Zhang Qingmei, Wang Xiaohong, Zhang Xuan, Zhan Jingfen, Zhang Binbin, Jia Jin, Chen Jie
Department of Gynecology, The People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350004, P.R. China.
Exp Ther Med. 2022 Aug 5;24(4):614. doi: 10.3892/etm.2022.11551. eCollection 2022 Oct.
Ovarian cancer (OV) affects hundreds of thousands of women worldwide each year. The delayed onset of symptoms and insufficient diagnostic options of OV are mainly responsible for its high mortality rate and poor prognosis in the patients. Transmembrane (TMEM) proteins are associated with human cancers, and multiple of them have been identified as oncogenic. TMEM14A is among this group. However, the function of TMEM14A in OV remains unclear. In the present study, it was aimed to find out the roles and underlying mechanism of TMEM14A in OV. RNA interference and lentiviral-mediate vector were used to induce TMEM14A silencing or overexpression. Flow cytometric analysis was used to examine cell apoptosis. Oxygen consumption and extracellular acidification were determined using Seahorse XF24 analyzer. Xenograft mice model was constructed to quantify the role of TMEM14A . Chromatin immunoprecipitation assay was used to determine the connection between TMEM14A and c-Myc. Immunohistochemical staining assay was applied to determine the expression pattern of TMEM14A and c-Myc in OV tissues. TMEM14A was revealed to be highly expressed in OV tumor and correlated with prognostic conditions in patients with OV. TMEM14A inhibited OV cell apoptosis while accelerate their energy metabolism, including glycolysis and oxygen respiration. TMEM14A was positively correlated with c-MYC. Overexpression of c-Myc rescued the function of TMEM14A. In conclusion, TMEM14A was recognized as both diagnostic and prognostic biomarker candidate for early detection of OV and improving the clinical management of patients with OV, which would also facilitate further mechanistic studies of TMEM proteins in OV tumorigenicity. Moreover, the present findings demonstrated that TMEM14A has the potential values as a molecular target in developing the therapy of human OV.
卵巢癌（OV）每年影响全球数十万女性。卵巢癌症状出现延迟以及诊断方法不足是其死亡率高和患者预后差的主要原因。跨膜（TMEM）蛋白与人类癌症相关，其中多种已被确定为致癌蛋白。TMEM14A就在这一组中。然而，TMEM14A在卵巢癌中的功能仍不清楚。在本研究中，旨在探究TMEM14A在卵巢癌中的作用及潜在机制。使用RNA干扰和慢病毒介导的载体来诱导TMEM14A沉默或过表达。采用流式细胞术分析检测细胞凋亡。使用海马XF24分析仪测定氧消耗和细胞外酸化。构建异种移植小鼠模型以量化TMEM14A的作用。采用染色质免疫沉淀试验确定TMEM14A与c-Myc之间的联系。应用免疫组织化学染色试验确定TMEM14A和c-Myc在卵巢癌组织中的表达模式。结果显示，TMEM14A在卵巢癌肿瘤中高表达，且与卵巢癌患者的预后情况相关。TMEM14A抑制卵巢癌细胞凋亡，同时加速其能量代谢，包括糖酵解和有氧呼吸。TMEM14A与c-MYC呈正相关。c-Myc的过表达挽救了TMEM14A的功能。总之，TMEM14A被认为是早期检测卵巢癌和改善卵巢癌患者临床管理的诊断和预后生物标志物候选物，这也将有助于进一步研究TMEM蛋白在卵巢癌发生中的机制。此外，本研究结果表明，TMEM14A作为人类卵巢癌治疗靶点具有潜在价值。
