Abstract
Fat mass and obesity-associated (FTO) protein has been identified as a critical demethylase in regulating cellular mRNA stability by removing N6-methyladenosine (m6A) residues in mRNA. Even though the role of FTO in body energy metabolism has been well established, its role in cancer cell homeostasis remains unclear. In the present study, by using RNA interference, it was indicated that FTO is required for pancreatic cancer cell proliferation. Knockdown of FTO resulted in compromised proliferation of pancreatic cancer cells. Furthermore, DNA synthesis was compromised, followed by an increase in apoptosis in FTO small interfering RNA (siRNA)-treated cells. In terms of its underlying mechanism, FTO has been indicated to interact with MYC proto-oncogene, bHLH transcription factor and to enhance its stability by decreasing its m6A level. Therefore, the aforementioned observations indicate a novel mechanism for the regulation of pancreatic cancer cells by FTO, which may provide insight on pancreatic cancer treatment strategies.