TMEM49 induced ovarian cancer via apoptosis pathway

Abstract

Ovarian cancer was one of the most lethal types of reproductive system tumors and a leading cause of cancer‐related death in women globally. The mechanism of ovarian cancer is poorly defined, in which apoptosis might play an important role. TMEM49, a 406 amino‐acid multi‐pass membrane protein localized to the endoplasmic reticulum‐Golgi intermediate compartment membrane, was identified to be involved in cancer‐relevant processes, and was demonstrated to inhibit proliferation and pulmonary metastasis of hepato‐cellular carcinoma, but little is known about the expression pattern and biological function of TMEM49 in ovarian cancer. Thus, in this study, we tested whether TMEM49 was associated with ovarian cancer and focused on the underlying mechanism by knocking down TMEM49 expression with siRNA in ovarian cells. In vivo, immuno‐histochemistry staining was performed and results showed TMEM49 was highly up‐regulated ovarian tissue of ovarian cancer patient when compared to patient with benign ovarian tumor. In viro,, with flow cytometry and CCK8 methods, SiRNA TMEM49 was demonstrated to inhibit cell proliferation, arrest G1/S transition, and induce cell apoptosis. Furthermore, western blot showed increased expression of apoptosis‐related protein such as Caspase3, Bad, and Bax, while expression metastasis‐related protein such as MMP2, KLF10, and CXCL12 were down‐regulated by TMEM49 knockdown. All these suggested that TMEM49‐related apoptosis play a role in ovarian cancer, and TMEM49 may be a potential therapeutic target in ovarian cancer.Over‐expression of TMEM49 in ovarian cancer. a The mRNA level of TMEM49 in ovarian and normal tissues. b TMEM49 expression was significantly increased inovarian tumor tissues when compared with normal tissues of patients from TCGA dataset. c TMEM49 expression was evaluated by immunohistochemistry inovarian and adjacent tissues.Figure 1