TMEM14A aggravates the progression of human ovarian cancer cells by enhancing the activity of glycolysis

TMEM14A通过增强糖酵解活性来加剧人类卵巢癌细胞的进展

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作者:Qingmei Zhang, Xiaohong Wang, Xuan Zhang, Jingfen Zhan, Binbin Zhang, Jin Jia, Jie Chen

Abstract

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 in vivo. 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.

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