Analysis of long non-coding RNA profiled following MC-LR-induced hepatotoxicity using high-throughput sequencing

Abstract

ABSTRACTThe occurrence of microcystin-LR(MC-LR) variant a known hepatotoxin constitutes a global public health concern. However, the molecular mechanisms underlying MC-LR-induced hepatotoxicity remain to be determined. The aim of this study was to investigate whether long noncoding RNAs (lncRNA) were involved in MC-LR-mediated hepatotoxicity using human normal liver cell line HL7702 to profile lncRNAs after 24 hr treatment with MC-LR. With the use of high-throughput sequencing techniques, data showed that the expression levels of 37, 33, 34, 35 lncRNA were significantly altered following exposure to 1, 2.5, 5, or 10 μM MC-LR, respectively. In particular, the expression levels of LINC00847, MIR22HG and LNC_00027 were markedly increased in all treatment groups. It is of interest that LNC_00027 was identified as a novel lncRNA. Quantitative real-time PCR (qPCR) was employed to determine the differentially expressed lncRNA levels. Analysis using Gene Ontology (GO) enrichment identified the functions of target genes involved in systems development, metabolism, and protein binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that MC-LR exposure upregulated some important signaling pathways including pathway in cancer, PI3K-AKT signaling and MAPK pathway. In summary, data indicate that the MC-LR-induced alterations in lncRNA may be associated with hepatotoxicity and that upregulation of LINC00847, MIR22HG and LNC_00027 may play important roles in the observed MC-mediated liver damage.