BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies with high morbidity and mortality worldwide. B3GNT6 as been predicted to serve as a prognostic indicator for CRC patients, but its biological function and underlying mechanism in CRC remain largely unclear. OBJECTIVE: Our investigation was designed to clarify the biological function and molecular mechanism of B3GNT6 in CRC progression. METHODS: The mRNA and protein expression levels of B3GNT6 in CRC tissues and cell lines were examined using RT-qPCR and western blot assay. CCK-8, flow cytometry, and TUNEL staining were used to evaluate cell proliferation, cell cycle distribution, and apoptosis in vitro and in vivo. The migratory and invasive abilities of cells were determined by Transwell assay. Cell autophagy was analyzed by immunofluorescence staining. The expression of apoptosis-related proteins and key components in the KRAS/ERK signaling pathway was detected using RT-qPCR and western blot analysis. RESULTS: B3GNT6 was significantly downregulated in CRC tissues and cell lines. Functionally, B3GNT6 overexpression inhibited cell proliferation, autophagy, migration, and invasion, induced G2 phase cell cycle arrest and apoptosis, whereas these effects were abolished by KRAS overexpression. In vivo experiments further confirmed that B3GNT6 overexpression suppressed tumor growth and autophagy, and promoted apoptosis. Mechanistically, B3GNT6 overexpression inhibited the activation of the KRAS/ERK signaling pathway, while upregulation of KRAS had the opposite effect. CONCLUSION: B3GNT6 inhibits colorectal cancer progression by blocking the KRAS/ERK signaling pathway. Thus, B3GNT6 may serve as a promising diagnostic and prognostic biomarker as well as a potential therapeutic target for CRC.
Jing et al. (Thu,) studied this question.