O-GlcNAcylation of CSNK2A1 by OGT is Involved in the Progression of Colorectal Cancer.

Abstract

Colorectal cancer (CRC) metastasis is challenging for improved clinical outcomes. The casein kinase 2 alpha 1 (CSNK2A1) is an oncogene involved in several cancers. This study aimed to investigate the influence of CSNK2A1 on CRC progression and the related molecular mechanism. The CSNK2A1 levels were predicted using bioinformatic analysis and were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Cell phenotypes were analyzed using cell-counting kit-8, colony formation, transwell assay, and western blot. Tumor growth was evaluated in a tumor-bearing mouse model in vivo. Similarly, O-GlcNAc modification of CSNK2A1 was assessed by immunoprecipitation, western blot, and immunofluorescence. Results indicated that CSNK2A1 was upregulated in CRC and was related to poor prognosis. Interference with CSNK2A1 suppressed CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition, inhibiting tumor growth. Moreover, OGT promoted the glycosylation modification of CSNK2A1, enhanced its protein stability, and reversed tumor progression when CSNK2A1 was knocked down. The CSNK2A1 might also affect CRC progression via the PI3K/AKT pathway. In conclusion, the OGT-O-GlcNAcylation-CSNK2A1 axis accelerated the malignant advancement of CRC, suggesting potential CRC therapeutic targets.