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09 March 2020 : Database Analysis  

Overexpression of Karyopherin Subunit alpha 2 (KPNA2) Predicts Unfavorable Prognosis and Promotes Bladder Cancer Tumorigenicity via the P53 Pathway

Changlong Shi1ABCDEF, Li Sun2C, Shaozhuang Liu1C, Enchong Zhang1C, Yongsheng Song1DG*

DOI: 10.12659/MSM.921087

Med Sci Monit 2020; 26:e921087

Abstract

BACKGROUND: 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.

MATERIAL AND METHODS: The RNA-seq data on BC from The Cancer Genome Atlas (TCGA) database were imported into R statistical software for differential analysis. 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 quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (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 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 associated with shorter 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, BCL2, and pro-caspase3 decreased significantly, whereas P53, P21, BAX, and cleaved-caspase3 increased significantly. The results in the overexpression group were the opposite of results in the knockdown group.

CONCLUSIONS: KPNA2 is an oncogenic factor that facilitates BC tumorigenicity through the P53 pathway.

Keywords: Apoptosis, Neoplasm Invasiveness, Prognosis, Urinary Bladder Neoplasms, Gene Knockout Techniques, Kaplan-Meier Estimate, Tumor Suppressor Protein p53, alpha Karyopherins

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750