Methylation at the N6 position of adenosine (m6A) is a post-transcriptional modification of mRNA. However, little is known regarding the biological meanings of this epigenetic regulation of mRNA. Recent technological advances have made it possible to detect mRNA methylation. The m6A was found near regulatory regions and its level is altered in various cancer cell lines. FTO, the fat mass and obesity associated gene, was recently shown as an m6A demethylase. FTO gene polymorphism has been associated with aggressive prostate cancer (PCA). We thus hypothesize that FTO and mRNA methylation play critical roles in PCA. To test this hypothesis, the proposed research aims to examine how FTO regulates PCA through m6A-modulated gene expression. Our data demonstrated that the levels of m6A and its modifying enzymes including FTO are de-regulated during prostate cancer progression. FTO regulates genes/pathways that play important roles in malignancy including wound response, DNA replication, inflammation, and transcription factor activities.
NETL
