Distinct 5-methylcytosine profiles of circular RNA in human hepatocellular carcinoma

Am J Transl Res. 2020 Sep 15;12(9):5719-5729. eCollection 2020.

Abstract

Recent studies have indicated that several circular RNAs (circRNAs) can affect the occurrence and development of hepatocellular carcinoma (HCC). Post-transcriptional methylation modifications, including 5-methylcytosine (m5C) modification, are closely related to the tumorigenesis of cancers. However, the map of m5C modification of circRNA in HCC remains to be investigated. In this study, we performed MeRIP-seq to identify m5C sites on circRNA of human HCC tissues and paired adjacent non-tumor tissues. Further, we analyzed the relationship between m5C and HCC. Moreover, we performed a bioinformatics analysis to predict the function of specific methylated transcripts. We found that there was a significant difference in m5C between HCC tissues and paired non-tumor tissues, suggesting potential critical roles of m5C of circRNA in HCC development. In addition, the Gene Ontology (GO) analysis results indicated that the unique distribution pattern of circRNA m5C in HCC was associated with specific metabolism-associated pathways. In conclusion, our findings suggest a possible association between HCC and m5C of circRNA. Additionally, our results provide new insights into a novel function of m5C RNA methylation of circRNA in HCC progression.

Keywords: 5-methylcytosine; MeRIP-seq; RNA methylation; circRNA; hepatocellular carcinoma.