KIF23 promotes cervical cancer progression via inhibiting NLRP3‐mediated pyroptosis

Author:

Liu Xiaoyan1ORCID,Xie Xiaoqing1ORCID,Li Qiulian1ORCID,Xie Xiaohong1ORCID,Xiong Min1ORCID,Han Wenling1ORCID,Xie Wei1ORCID

Affiliation:

1. Department of Obstetrics and Gynecology First Affiliated Hospital of Gannan Medical University Ganzhou City Jiangxi Province China

Abstract

AbstractBackgroundCervical cancer (CC), closely linked to persistent human papillomavirus infection, represents a major health problem for women worldwide. The objective of this study is to elucidate KIF23's role in the development of CC and its regulatory mechanism.MethodsThe bioinformatics methods were utilized to extract pyroptosis‐associated differentially expressed genes (DEGs) and pivot genes from the GSE9750 and GSE63678 datasets, followed by immune infiltration analysis and quantification of these genes' expression. The effects of kinesin family member 23 (KIF23) were verified through functional experiments in vitro and a mouse xenograft model. The NLPR3 activator, nigericin, was applied for further analyzing the potential regulatory mechanism of KIF23 in CC.ResultsA total of 8 pyroptosis‐related DEGs were screened out, among which 4 candidate core genes were identified as candidate hub genes and confirmed upregulation in CC tissues and cells. These genes respectively showed a positive correlation with the infiltration of distinct immune cells or tumor purity. Downregulation of KIF23 could suppress the proliferation, migration, and invasion abilities in CC cells and tumorigenesis through enhancing pyroptosis. Conversely, KIF23 overexpression accelerated the malignant phenotypes of CC cells and inhibited pyroptosis activation, which was blocked by nigericin treatment.ConclusionsKIF23 may play an oncogenic role in CC progression via inhibition of the NLRP3‐mediated pyroptosis pathway.

Publisher

Wiley

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