Circular RNA expression profiles following MC-LR treatment in human normal liver cell line (HL7702) cells using high-throughput sequencing analysis

Abstract

ABSTRACTMicrocystin-LR (MC-LR), a frequently occurring hepatotoxic cyanotoxin produced by cyanobacterial blooms, poses a great threat to human health. However, the precise molecular mechanisms underlying MC-LR-induced hepatotoxicity remain to be determined. Recent investigators found that in many human diseases circular RNAs (circRNAs) a class of endogenous non-coding RNAs played critical roles in disease outcomes. The aim of this study was to investigate whether circRNAs were involved in MC-LR-mediated hepatotoxicity using human normal liver cell line (HL7702). Using high-throughput sequencing analysis data demonstrated that expression levels of 3250, 3111, 3097, 3253 circRNAs were significantly altered at concentrations ranging from 1 to 10 µM MC-LR. Expression levels of hsa_circRNA_0000657 and hsa_circRNA_0000659 were down-regulated while hsa_circRNA_0003247 and hsa_circRNA_0001535 were up-regulated in all MC-LR-exposed groups. The high-throughput sequencing results of selected circRNAs differential expression genes (DEGs) levels were verified by real-time fluorescent quantitative PCR (qRT-PCR). Gene Ontology (GO) enrichment analysis showed that the functions of circRNAs significantly altered in HL7702 cells were predominantly associated with metabolism, systems development, and protein binding. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis data revealed that the target genes of differentially expressed circRNAs in HL7702 cells were involved in FoxO signaling pathway, protein processing in endoplasmic reticulum, Ras signaling pathway, cell cycle, PI3K-Akt signaling pathway, MAPK signaling pathway and pathways in cancer. In summary, evidence indicates that a correlation may exist between circRNAs and MC-LR-induced hepatotoxicity.