m(6)A-modified circRNA MYO1C participates in the tumor immune surveillance of pancreatic ductal adenocarcinoma through m(6)A/PD-L1 manner

Emerging evidence indicates the critical roles of N(6)-methyladenosine (m(6)A) modification in human cancers. Herein, our work reported that a novel m(6)A-modified circRNA from the MYO1C gene, circMYO1C, upregulated in the pancreatic ductal adenocarcinoma (PDAC). Our findings demonstrated that circMYO1C is highly expressed in PDAC tissues. Functionally, circMYO1C promoted the proliferation and migration of PDAC cells in vitro and its silencing reduced the tumor growth in vivo. Mechanistically, circMYO1C cyclization was mediated by m(6)A methyltransferase METTL3. Moreover, methylated RNA immunoprecipitation sequencing (MeRIP-seq) unveiled the remarkable m(6)A modification on PD-L1 mRNA. Moreover, circMYO1C targeted the m(6)A site of PD-L1 mRNA to enhance its stability by cooperating with IGF2BP2, thereby accelerating PDAC immune escape. In conclusion, these findings highlight the oncogenic role of METTL3-induced circMYO1C in PDAC tumorigenesis via an m(6)A-dependent manner, inspiring a novel strategy to explore PDAC epigenetic therapy.