Centromere protein A knockdown inhibits rectal cancer through O6- methylguanine DNA methyltransferase/protein tyrosine phosphatase nonreceptor type 4 axis  

作　　者：Ming-Jie Xin Yong Yuan 

机构地区：[1]Medical College,Henan Vocational University of Science and Technology,Zhoukou 466000,Henan Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2025年第4期347-364,共18页世界胃肠肿瘤学杂志(英文)

基　　金：This study was reviewed and approved by the Ethic Committee of Medical College of Henan Vocational University of Science and Technology(Approval No.HVUYL414101416920231017001);all participants signed a written informed consent.

摘　　要：BACKGROUND Centromere protein A(CENPA)exhibits an increased expression level in primary human rectal cancer tissues,but its role has not been investigated.AIM To clarify the specific role and mechanism of CENPA in rectal cancer progression.METHODS CENPA protein expression in rectal cancer tissues and cell lines were detected.CENPA was overexpressed and knocked down in SW837 and SW480 cells,and proliferation,invasion,apoptosis and epithelial-mesenchymal transition(EMT)marker protein levels were examined.O6-methylguanine DNA methyltransferase(MGMT)promoter methylation was assessed with methylation-specific poly-merase chain reaction.Co-immunoprecipitation assay verified the interaction between MGMT and protein tyrosine phosphatase nonreceptor type 4(PTPN4).SW837 cells with CENPA knockdown were injected subcutaneously into mice,and tumor growth was examined.RESULTS CENPA was upregulated in rectal cancer tissues and cell lines.CENPA overex-pression promoted proliferation,invasion and EMT,and inhibited apoptosis in rectal cancer cells.Whereas CENPA knockdown showed the opposite results.Moreover,CENPA inhibited MGMT expression by promoting DNA methyltrans-ferase 1-mediated MGMT promoter methylation.MGMT knockdown abolished the CENPA knockdown-mediated inhibition of rectal cancer cell progression.MGMT increased PTPN4 protein stability by inhibiting PTPN4 ubiquitination degradation via competing with ubiquitin-conjugating enzyme E2O for interacting with PTPN4.PTPN4 knockdown abolished the inhibitory effects of MGMT overexpression on rectal cancer cell progression.Moreover,CENPA knockdown inhibited xenograft tumor growth in vivo.CONCLUSION CENPA knockdown inhibited rectal cancer cell growth and attenuated xenograft tumor growth through regulating the MGMT/PTPN4 axis.

关 键 词：Rectal cancer Centromere protein A O6-methylguanine DNA methyltransferase Protein tyrosine phosphatase nonreceptor type 4 PROLIFERATION INVASION 

分 类 号：R73[医药卫生—肿瘤]