NLRC5 promotes tumorigenesis by regulating the PI3K/AKT/autophagy pathway in cervical cancer

Abstract Background NLR Family CARD Domain Containing 5, (NLRC5) plays an important role in tumorigenesis. However, its effect in cervical cancer (CC) remains unclear. This study was aimed to investigate the function of NLRC5 on CC. Methods The expression of NLRC5 as well as LC3 and Beclin1 were detected by immunohistochemical SP method. The relationships between the NLRC5 expression and the clinicopathological parameters of the patents were analyzed with rank sum test. Kaplan-Meier survival curve was used to analyze the correlation between NLRC5, LC3, Beclin1 expression and the clinical prognosis. In addition, univariate analysis and multivariate survival analysis were used to examine the effect of NLRC5 on prognosis. The function of NLRC5 in CC was validated by CCK8 assay and Transwell assay using Hela cell with knowdown or over-expressed NLRC5. The regulation mechanism of NLRC5 was investigated by western blot. Results We found that NLRC5 was down-regulated in CC tissues compared with normal cervical tissues. Patients with higher NLRC5 expression, age, HPV infection, lymph node metastasis, recurrence and histological grade had better prognosis independently. Univariate and multivariate analyses showed NLRC5 was a prognostic factor for CC. Pearson correlation analysis showed NLRC5 may exert its function in CC by autophagy related proteins especially for LC3. In vitro cell experiment proved that NLRC5 regulated the level LC3 and promoted the proliferation, migration and invasion of cervical cancer cell by activating AKT signaling pathway. In the presence of AKT signaling pathway inhibitor LY294002, the positive role of NLRC5 in proliferation, migration, and invasion of cervical cancer cell was restricted. Conclusions These findings presented NLRC5 may as a promising predictor in patients with cervical cancer. Additionally, NLRC5 regulate LC3 expression to promote HeLa cell proliferation, migration and Invasion by activating the AKT Signaling Pathway.