Genome-wide identification and characterization of circular RNA m 6 A modification in pancreatic cancer

Background N 6 -methyladenosine (m 6 A) is the most abundant modification of RNA in eukaryotic cells and play critical roles in cancer. While most related studies focus on m 6 A modifications in linear RNA, transcriptome-wide profiling and exploration of m 6 A modification in circular RNAs in cancer is still lacking. Methods For the detection of m 6 A modification in circRNAs, we developed a new bioinformatics tools called Circm6A and applied it to the m 6 A-seq data of 77 tissue samples from 58 individuals with pancreatic ductal adenocarcinoma (PDAC). Results Circm6A performs better than the existing circRNA identification tools, which achieved highest F1 score among these tools in the detection of circRNAs with m 6 A modifications. By using Circm6A, we identified a total of 8807 m 6 A-circRNAs from our m 6 A-seq data. The m 6 A-circRNAs tend to be hypermethylated in PDAC tumor tissues compared with normal tissues. The hypermethylated m 6 A-circRNAs were associated with a significant gain of circRNA-mRNA coexpression network, leading to the dysregulation of many important cancer-related pathways. Moreover, we found the cues that hypermethylated m 6 A-circRNAs may promote the circularization and translation of circRNAs. Conclusions These comprehensive findings further bridged the knowledge gaps between m 6 A modification and circRNAs fields by depicting the m 6 A-circRNAs genomic landscape of PDAC patients and revealed the emerging roles played by m 6 A-circRNAs in pancreatic cancer. Circm6A is available at https://github.com/canceromics/circm6a .