Study On The Function Of Fat Mass And Obesity-associated Protein In Pancreatic Cancer Cell

Objective:Recently,Fat mass and obesity-associated(FTO)protein has been identified as a critical demethylase to regulate cellular mRNA stability via removing N6-methyladenosine(m6A)residues in mRNA.Although its roles in body energy metabolism has been well established,it roles in cancer cell homeostasis remain undetermined.Methods:In the present study,the function of FTO in pancreatic cancer was study by using RNA interference.Cell proliferation was detected by MTT and BrdU assays.Cell apoptosis was detected by TUNEL.The mRNA expression was measured by RT-qPCR.The protein expression was measured by WB.The interaction between FTO protein and c-Myc mRNA was captured by RIP.Dot blot assay was used to measured the RNA m6A.Results:We found that FTO is required for pancreatic cancer cell proliferation.Knockdown of FTO resulted in compromised proliferation in pancreatic cancer cells.Furthermore,DNA synthesis was compromised,followed by increased apoptosis in FTO siRNA-treated cells.Mechanistically,FTO interacted with c-Myc mRNA and its knockdown resulted in increased m6A levels in c-Myc.Taken together,these data indicate a novel mechanism for the regulation of pancreatic cancer cell,which may shed new lights on novel pancreatic cancer treatment strategies.Conclusion:The highly expressed FTO protein can promote cells proliferation and inhibit apoptosis in pancreatic cancer cells.FTO protein interacted with mRNA and stabilized the expression of c-myc mRNA.