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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13073-021-01002-w.