KIAA1429 promotes the malignancy of oral squamous cell carcinoma by regulating CA9 m6A methylation

Abstract

KIAA1429 has been reported as a cancer regulator, but its role and mechanism in the progression of oral squamous cell carcinoma (OSCC) remain elusive. The objective of the present research was to figure out the effect of KIAA1429 regulated CA9 on the progression of OSCC. Using qRT-PCR and bioinformatics analysis, we studied the expression levels of KIAA1429 and CA9 in OSCC tissue samples. The functional roles of KIAA1429 and CA9 were assessed using transwell and CCK-8 assays. The regulation among KIAA1429 and CA9 was investigated using MeRIP and western blotting assays. In addition, the m6A level in OSCC was measured utilizing RNA m6A quantification. In OSCC, KIAA1429 and m6A levels were upregulated. We observed that KIAA1429 inhibition declined proliferation, migration, and invasion of OSCC cells and decreased cell growth in vivo. Furthermore, KIAA1429 serves as a crucial upstream regulator of CA9 in OSCC and upregulates CA9 expression through an m6A-dependent mechanism. We observed that CA9 was upregulated in OSCC samples and that low expression of KIAA1429 partially restored the enhanced malignant phenotype caused by CA9 overexpression. Overall, our findings suggest that KIAA1429 and CA9 act as pro-oncogenic factors in OSCC, with KIAA1429 promoting OSCC malignancy through m6A modification-dependent stabilization of CA9 transcripts, which represents a novel regulatory mechanism in OSCC.