m6A methylation of circKPNA2 promotes colorectal carcinogenesis by activating the RIN1-Ras pathway.

Colorectal cancer (CRC) is a prevalent and highly lethal malignancy. However, the molecular mechanisms underlying its progression remain incompletely understood. Therefore, this study aimed to investigate the role and mechanisms of circKPNA2 in CRC progression. We used various techniques, including RNA sequencing, functional assays, RNA pull-down, and mass spectrometry, to examine the expression and function of circKPNA2. Our findings indicate that circKPNA2 is significantly upregulated in CRC tissues and cell lines. It contributes to tumour growth by promoting cell proliferation, migration, and invasion. We found that circKPNA2 specifically binds to the RIN1 protein and increases its levels, thereby activating the Ras signalling pathway and facilitating CRC progression. Additionally, we identified that METTL3 regulates the expression of circKPNA2 through N6-methyladenosine (m6A) methylation, which in turn affects CRC cell proliferation, migration, and invasion. These results deepen our understanding of CRC biology and underscore the potential of targeting circKPNA2 as both a therapeutic target and a diagnostic biomarker to improve CRC diagnosis and treatment.