CNOT7 modulates biological functions of ovarian cancer cells via AKT signaling pathway

Abstract

AimsCNOT7 plays an important role in many biological processes, providing attractive opportunities for the treatment of malignant tumors. However, the functions and mechanism of CNOT7 in ovarian cancer (OC) have not been elucidated. The purpose of this study was to assess the role of CNOT7 in OC. Materials and methodsSKOV3 and A2780 cells were chosen as the cell lines for the experiments of this manuscript via the analysis of the expression of CNOT7 protein and the mRNA level in ovarian surface epithelium (OSE) cells, SKOV3, HO8910 and A2780 cells. The expression of CNOT7 was detected by western blot assays and RT-PCR in A2780 and SKOV3 cells. The MTT assays, colony formation assays and EdU assays were used to measure cell proliferation when CNOT7 was knocked down or overexpressed in A2780 and SKOV3 cells. Furthermore, cell migration and invasion ability were achieved from transwell assays. Cell cycle and apoptosis rate after small interference RNA-CNOT7 (siRNA-CNOT7) were detected by flow cytometry assays. Finally, the cell proliferation, migration and invasion ability were detected when A2780 and SKOV3 cells with CNOT7 overexpression were treated with LY294002. Key findingsThe expression of CNOT7 protein in OC cells, including SKOV3, HO8910 and A2780 cells were significantly higher than that in OSE cells (P < 0.05). The mRNA level of CNOT7 in HO8910 and A2780 cells were significantly higher than that in OSE cells (P < 0.01). However, the mRNA level of CNOT7 in SKOV3 cells was no significant difference compared with OSE cells (P > 0.05). The results suggested that knockdown of CNOT7 could inhibit the cell proliferation, migration and invasion ability in A2780 and SKOV3 cells, and increase cell apoptosis and autophagy. The expression of apoptosis-related molecules (PARP, Caspase3 and Caspase9) and autophagy-related protein (LC3B) were up-regulated after CNOT7 knockdown, while the expression of cycle-related protein (CDK6) and the anti-apoptotic gene (Bcl2) were downregulated. Meanwhile, the opposite results were observed when CNOT7 was overexpressed in A2780 and SKOV3 cells. It is worth noting that the effect of CNOT7 overexpression in A2780 and SKOV3 cells could be partially or completely eliminated by treatment with AKT inhibitor LY294002. SignificanceCNOT7 has a carcinogenic effect in OC, and the carcinogenic effect may be achieved via the AKT signaling pathway.