ArticleWorld journal of gastrointestinal oncology2025
Centromere protein A knockdown inhibits rectal cancer through O6-methylguanine DNA methyltransferase/protein tyrosine phosphatase nonreceptor type 4 axis.
Article in World journal of gastrointestinal oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCentromere protein A (CENPA) exhibits an increased expression level in primary human rectal cancer tissues, but its role has not been investigated.
aimTo clarify the specific role and mechanism of CENPA in rectal cancer progression.
methodsCENPA 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 polymerase 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.
resultsCENPA was upregulated in rectal cancer tissues and cell lines. CENPA overexpression 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 methyltransferase 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
conclusionCENPA knockdown inhibited rectal cancer cell growth and attenuated xenograft tumor growth through regulating the MGMT/PTPN4 axis.
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