Effect of Humantenine on mRNA m6A Modification and Expression in Human Colon Cancer Cell Line HCT116.

Abstract

Humantenine, an alkaloid isolated from the medicinal herb Gelsemium elegans (Gardner & Chapm.) Benth., has been reported to induce intestinal irritation, but the underlying toxicological mechanisms remain unclear. The object of the present study was to investigate the RNA N6-methyladenosine (m6A) modification and distinct mRNA transcriptome profiles in humantenine-treated HCT116 human colon cancer cells. High-throughput MeRIP-seq and mRNA-seq were performed, and bioinformatic analysis was performed to reveal the role of abnormal RNA m6A modification and mRNA expression in humantenine-induced intestinal cell toxicity. After humantenine treatment of HCT116 cells, 1401 genes were in the overlap of differentially m6A-modified mRNA and differentially expressed mRNA. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology annotation terms for actin cytoskeleton, tight junctions, and adherens junctions were enriched. A total of 11 kinds of RNA m6A methylation regulators were differentially expressed. The m6A methylation levels of target genes were disordered in the humantenine group. In conclusion, this study suggested that the HCT116 cell injury induced by humantenine was associated with the abnormal mRNA expression of m6A regulators, as well as disordered m6A methylation levels of target genes.