Abstract: Objective The objectives of this study were to investigate the expression of SKA1 in renal cell carcinoma(RCC)and its effect on cell proliferation and apoptosis of RCC as well as its molecular mechanism.Methods The data set of RCC was collected from the Cancer Genome Atlas(TCGA).The expression of SKA1 in renal cell carcinoma tissues and normal renal tissues,and its relationship with clinicopathological characteristics and prognosis were analyzed.The samples of 72 patients with RCC were collected from the Affiliated Tumor Hospital of Xinjiang Medical University from January 2016 to September 2018.The expression of SKA1 was detected by quantitative real-time PCR.786-O and ACHN cells were transfected with lentivirus vector(shSKA1)and control virus vector(shNC),respectively.A CCK-8 assay was used to detect cell proliferation;a colony formation assay was used to detect the ability of cell clone formation;annexin V-FITC was used to detect the apoptotic rate.IPA@ online bioinformatics software was used to analyze the signal transduction pathway and biological function of differential genes detected by gene expression profile chip.The levels of TNF-α,cleaved-caspase-3,cleaved-caspase-9,p-Akt,and p-mTOR proteins were detected by Western blot.Results The expression of SKA1 in RCC was significantly higher than that in normal renal tissues(P＜0.01),which was related to T,N,M(TNM)and AJCC stages of renal clear cell carcinoma and renal papillary cell carcinoma(P＜0.01).The overall survival time of patients with high expression of SKA1 was significantly shorter than that of patients with low expression of SKA1(P＜0.001).The results of tissue sample study confirmed that the expression of SKA1 in renal clear cell carcinoma was higher than that in adjacent tissues,which was consistent with the results of TCGA database analysis.Compared with the control group,the proliferation of RCC cells transfected with shSKA1 lentivirus decreased significantly,and the proportion of apoptotic cells increased(P＜0.01).IPA@ analysis showed that cell growth and proliferation ranked the first in terms of biological function enrichment,TNF was strongly activated,and PI3K/Akt/mTOR signaling molecules were significantly inhibited.The results of Western blot showed that the expression of TNF-α,cleaved-caspase-3 and cleaved-caspase-9 in the SKA1 interference group was significantly increased,while the phosphorylation levels of Akt and mTOR,which were related to cell proliferation,were significantly down-regulated,which was consistent with enrichment analysis result.Conclusion SKA1 is a poor prognostic factor for RCC.The mechanism may be related to the activation of TNF-α and the inhibitory phosphorylation of PI3K/Akt/mTOR pathway.

Key words: Renal cell carcinoma, SKA1, Cell proliferation and apoptosis, Molecular mechanism