NCCRP1 promotes ovarian cancer progression and is associated with activation of the PI3K/AKT/mTOR signaling pathway and altered mitochondrial respiration.

Non-specific cytotoxic cell receptor protein 1 (NCCRP1) is a membrane protein involved in cell proliferation, but its role in ovarian cancer (OC) progression remains unclear. In this study, a prognostic model for OC was constructed using LASSO-penalized Cox regression analysis. NCCRP1 expression in ovarian tissues was detected by immunohistochemical staining, and its associations with clinicopathological features and prognosis were analyzed. The effects and underlying mechanism of NCCRP1 on the malignant biological behaviors of OC cells were further investigated in vitro and in vivo. The prognostic model consisted of 28 genes with significant prognostic value. Among these genes, NCCRP1 mRNA showed differential expression in ovarian tissues and potential prognostic significance. NCCRP1 protein was overexpressed in OC tissues compared with adjacent ovarian tissues, and high NCCRP1 expression was associated with ascites, tumor cells in ascites, lymph node metastasis, distant metastasis and advanced FIGO stage. Patients with high NCCRP1 expression tended to have poorer overall survival. Knockdown of NCCRP1 inhibited the proliferation, migration and invasion of OC cells and promoted apoptosis, whereas NCCRP1 overexpression produced the opposite effects. In addition, NCCRP1 knockdown decreased oxygen consumption rate, whereas NCCRP1 overexpression produced the opposite effect. NCCRP1 expression was also positively associated with the phosphorylation levels of PI3K, AKT and mTOR. These findings suggest that NCCRP1 promotes malignant biological behaviors in OC, is associated with altered mitochondrial respiratory activity and may exert its tumor-promoting effects, at least in part, through activation of the PI3K/AKT/mTOR signaling pathway. Therefore, NCCRP1 may serve as a novel prognostic marker and potential therapeutic target for OC patients.