Deregulation and delocalization of the m6A demethylase FTO and aberrant m6A levels in ccRCC tissue samples

N6-methyladenosine (m6A) is one of the most abundant mRNA modifications established by the activity of three classes of enzymes: writers, readers, and erasers. The relevance of m6A in the regulation of gene expression implies its key role in normal biological processes and cancer development. Given the little knowledge about the involvement of m6A in clear cell Renal Carcinoma (ccRCC), our analysis should be regarded as a pilot study aimed at investigating the expression of m6A enzymes in tissues and urine specimens of ccRCC patients. The expression of m6A enzymes was validated by quantitative reverse-transcription PCR and immunohistochemistry, comparing normal and tumoral tissues. Quantification of m6A levels in urine specimens of healthy and cancer patients was performed by colorimetric Urine m6A assay. We observed the upregulation and nuclear localization of the m6A demethylase FTO in tumoral tissues compared with their respective normal counterparts. The nuclear expression of FTO decreases with an increase in tumor grade. Moreover, we identified a decrease in m6A levels in cancer samples. These findings might represent novel evidence to further investigate the issue, to reveal new diagnostic markers for tumorigenesis, leading to a potential m6A-targeted therapy in ccRCC.