Background: Long non-coding RNAs (lncRNAs) and their N6-methyladenosine (M6A) modifications are involved in cancer occurrence and development.

Methods: lncRNA M6A modification in colorectal cancer (CRC) was comprehensively analyzed for the first time.

Results: M6A levels of lnRNAs in CRC tissues were higher than those in tumor-adjacent normal tissues. A total of 8,332 M6A peaks were detected in 6,690 lncRNAs in CRC tissues. Approximately 91% of the modified lncRNAs had unique M6A modification peaks. A total of 383 lncRNAs were differentially methylated in CRC, of which 48.24% had a length of 1-1,000 bp. Most of these were located on chromosomes 1, 2, 7, 11, 16 and 19; 42.3% were within a sense-overlapping exon. RNA sequencing identified 163 differentially expressed lncRNAs in CRC. GO and KEGG analyses revealed that genes near differentially-methylated or -expressed lncRNAs were associated with CRC occurrence and development. Methylation was positively correlated with lncRNA expression levels in CRC and tumor-adjacent normal tissues. More unmethylated than M6A methylated lncRNA molecules were detected. A competing endogenous RNA (ceRNA) and lncRNA-mRNA expression-regulation network revealed a regulatory relationship between lncRNAs, microRNAs (miRNAs), and mRNAs.

Conclusions: The findings may help improve our understanding of lncRNA function in colorectal cancer.