hnRNPA2B1 drives colorectal cancer progression via the circCDYL/EIF4A3/PHF8 axis.

Abstract

The RNA-binding protein hnRNPA2B1 acts as an m6A reader and plays a role in tumor development. This study investigates the potential mechanism of hnRNPA2B1 in colorectal cancer (CRC) progression. The expression profiles of hnRNPA2B1, circCDYL, and PHF8 in CRC cell lines were analyzed. Following si-hnRNPA2B1 transfection, CRC cell proliferation, invasion, and migration were evaluated by CCK-8 and Transwell. CDYL expression was detected after actinomycin D and RNase R treatment. RIP was conducted to assess the enrichment of hnRNPA2B1 and m6A on circCDYL. RIP and RNA pull-down assays established the interaction between circCDYL and EIF4A3/PHF8. EIF4A3 expression was evaluated using RT-qPCR and Western blot techniques. hnRNPA2B1 and PHF8 displayed high expression levels, whereas circCDYL showed low expression levels in colorectal cancer cells. Inhibition of hnRNPA2B1 reduced CRC cell proliferation, migration, and invasion. hnRNPA2B1 mechanistically elevated the m6A level of circCDYL while decreasing its expression, which in turn reduced the binding of circCDYL to EIF4A3 and enhanced PHF8 expression. In summary, hnRNPA2B1-mediated m6A modification decreases circCDYL expression, which inhibits the interaction of circCDYL with EIF4A3, enhances PHF8 expression, and ultimately facilitates CRC progression.