Overexpression Of Karyopherin Subunit Alpha2(KPNA2)Predicts Unfavorable Prognosis And Promotes Bladder Cancer Proliferation And Invasion Via The P53 Pathway

Objective: We sought to investigate the expression of KPNA2 in bladder cancer(BC)and its relationship with prognosis,and to analyze the potential mechanism of KPNA2 in promoting BC progression.Materials and methods: The RNA-seq data on BC from The Cancer Genome Atlas(TCGA)database were imported into R statistical software for differential analysis,and the target gene KPNA2 with obvious differential expression was selected as the research object.The clinical data for patients with BC were screened and analyzed with R software.The survival curve was drawn with the Kaplan-Meier Plotter.The expression of KPNA2 in 4 human BC cell lines and a human bladder epithelial cell line was detected by Real-Time quantitative Polymerase Chain Reaction(RT-qPCR)and Western blotting(WB).Transfected T24 and 5637 cell lines,KPNA2 gene was knocked down and overexpressed,and the transfection results were verified by RT-qPCR and WB.The proliferation of BC cells was detected with Cell Counting Kit-8(CCK8),detection of apoptosis,and flow cytometry,and the migration and invasion of BC cells were detected through Transwell assays.WB was used to detect the expression of proteins involved in the p53 pathway.Results: The expression of KPNA2 was higher in BC.The difference in KPNA2 expression was associated with many clinicopathological factors,and high expression of KPNA2 was related to poorer survival time.After KPNA2 knockout,the proliferation,migration,and invasion ability decreased significantly,the cell cycle was clearly arrested in the G0/G1 phase,and the number of apoptotic cells increased.Moreover,CyclinD1,BCL 2,and pro-caspase 3 decreased significantly,whereas p53,Tumor Protein p21(p21),BCL 2 Associated X(BAX),and cleaved-caspase 3 increased significantly.The results in the overexpression group were the opposite of results in the knockdown group.Conclusion: KPNA2 is an oncogenic factor that facilitates BC proliferation and invasion via the p53 pathway.