Pancreatic cancer is the deadliest malignancy of the digestive system and is the 
seventh most common cause of cancer-related deaths worldwide. The incidence and 
mortality of pancreatic cancer continue to increase, and its 5-year survival 
rate remains the lowest among all cancers. N6-methyladenine (m6A) is the most 
abundant reversible RNA modification in various eukaryotic messenger and long 
noncoding RNAs and plays crucial roles in the occurrence and development of 
cancers. However, the role of m6A in pancreatic cancer remains unclear. The 
present study aimed to explore the role of m6A and its regulators in pancreatic 
cancer and assess its underlying molecular mechanism associated with pancreatic 
cancer cell proliferation, invasion, and metastasis. Reduced expression of the 
m6A demethylase, fat mass and obesity-associated protein (FTO), was responsible 
for the high levels of m6A RNA modification in pancreatic cancer. Moreover, FTO 
demethylated the m6A modification of praja ring finger ubiquitin ligase 2 
(PJA2), thereby reducing its mRNA decay, suppressing Wnt signaling, and 
ultimately restraining the proliferation, invasion, and metastasis of pancreatic 
cancer cells. Altogether, this study describes new, potential molecular 
therapeutic targets for pancreatic cancer that could pave the way to improve 
patient outcome.