Integrated profiling of long non-coding RNAs and mRNAs identifies novel regulators associated with liver fibrosis

Abstract

Liver fibrosis is the underlying cause of cirrhosis and liver failure in any type of chronic liver injury. However, the function of lncRNAs in liver fibrosis is largely unknown. In this study, we performed transcriptome sequencing of CCl4 induced mouse fibrotic liver tissues and normal liver tissues, and found 118 lncRNAs and 1921 mRNAs were significantly up-regulated, whereas 59 lncRNAs and 1504 mRNAs were down-regulated in fibrotic livers. Gene ontology analysis revealed that the differentially expressed lncRNAs are implicated in cell junction, cell differentiation and cell proliferation, pathways closely associated with EMT. The co-expression network of highly conserved lncRNAs and highly co-expressed mRNAs were constructed, whose differential expression were further confirmed by quantitative real-time PCR. Two highly conserved lncRNAs, Gm11149 and Gm20471, were identified to be significantly up-regulated in liver fibrosis. Their target genes, Ncam1 and Prrx1 respectively, are important modulators of EMT. Thus, the relative dynamic levels of Gm11149 and Ncam1, Gm20471 and Prrx1 were further monitored during the progress of liver fibrosis and their co-expression pattern was proved. Collectively, our results uncovered a crucial role of lncRNAs in the regulation of liver fibrosis and the lncRNA -mRNA network might provide new therapeutic strategies.