The Effects Of KIF18B On Proliferation And Migration Of Prostate Cancer Based On Weighted Gene Co-expression Network Analysis

Objectives To determine key genes closely related to the clinicopathological characteristics of prostate cancer by WGCNA and evaluate the effects of KIF18 B on proliferation and migration of prostate cancer cells.Method Data were downloaded from the GEO database and analyzed by WGCNA,modules that closely related to clinicopathological characteristics were screened based on correlation coefficient R and P-value.PPI analysis was performed to determine the key genes in the selected module.The identified key genes were validated by the TCGA database.Finally,KIF18 B was selected as the targeted gene for the following analyses based on the results of gene co-expression and correlation analyses.shRNA technique was utilized to knock down the expression of KIF18B;q PCR and Western blot were utilized to determine the knockdown efficiency of KIF18 B.MTT,flow cytometry,wound healing assay and Transwell assay were utilized to determine the effects of KIF18 B on the proliferation,migration,invasion and apoptosis of prostate cancer cells.Gene expression profile chip was utilized to determine the differentially expressed genes after KIF18 B knockdown.Pathway enrichment analysis was performed and the PPI network was constructed.Results A total of 13 modules were identified by WGCNA.The magenta module was significantly correlated with all clinicopathological parameters(all P value<0.05).Key genes in magenta analyses were utilized for the construction of the PPI network.The results demonstrated that KIF4 A and KIF20 A were key genes in the magenta module.The results of Consensus Path DB revealed that the genes in the magenta module were mainly enriched in cell cycle signaling pathway.KIF18 B,KIF4A,KIF20 A,and KIF25 were found to be significantly differentially expressed in prostate cancer and para-cancer tissues in the TCGA database(all P value<0.05).The results of gene co-expression analysis and correlation analysis demonstrated that KIF18 B has a close co-expression relationship and correlation expression pattern with KIF4 A and KIF20A(P<0.05).Therefore,KIF18 B was selected for the following analyses.KIF18 B was found highly expressed in prostate cancer tissues in the TCGA database(P<0.05)and closely correlated with disease-free survival(P<0.05).In vitro assays demonstrated that the proliferation,migration and invasion were significantly attenuated and apoptosis was promoted after the knockdown of KIF18 B.The PPI network was used to determine key genes after the KIF18 B knockdown.The results demonstrated key genes were POLR2 E,HSPA8,CCNA2,PCNA,CDC6,MCM7,JAK1,RNF111,RFC3,and SNRPF.The results of survival analyses demonstrated that CCNA2,SNRPF,CDC6,and MCM7 were closely correlated with overall survival and disease-free survival of prostate cancer(all P value<0.05).Conclusion KIF18 B was highly expressed in prostate cancer and correlated with disease-free survival and clinicopathological parameters of prostate cancer.KIF18 B promotes the proliferation and migration,and attenuates the apoptosis of prostate cancer cells.CCNA2,SNRPF,CDC6,and MCM7 may be the key genes after KIF18 B knockdown and correlated with poor overall survival and disease-free survival of prostate cancer.