Analysis and verification of N (6)-methyladenosine-modified genes as novel biomarkers for clear cell renal cell carcinoma

N (6)-methyladenosine (m(6)A) has been involved in diverse biological processes in cancer, but its function and clinical value in clear cell renal cell carcinoma (ccRCC) remain largely unknown. In this study, we found that 1453 m(6)A-modified differentially expressed genes (DEGs) of ccRCC were mainly enriched in cell cycle, PI3K-AKT, and p53 signaling pathways. Then we constructed a co-expression network of the 1453 m(6)A-modified DEGs and identified a most clinically relevant module, where NUF2, CDCA3, CKAP2L, KIF14, and ASPM were hub genes. NUF2, CDCA3, and KIF14 could combine with a major RNA m(6)A methyltransferase METTL14, serving as biomarkers for ccRCC. Real-time quantitative PCR assay confirmed that NUF2, CDCA3, and KIF14 were highly expressed in ccRCC cell lines and ccRCC tissues. Furthermore, these three genes were modified by m(6)A and negatively regulated by METTL14. This study revealed that NUF2, CDCA3, and KIF14 were m(6)A-modified biomarkers, representing a potential diagnostic, prognostic, and therapeutic target for ccRCC.