Genome-wide identification of long noncoding RNAs in CCl(4)-induced liver fibrosis via RNA sequencing

Liver fibrosis occurs as a result of chronic liver lesions, which may subsequently develop into liver cirrhosis and hepatocellular carcinoma. The involvement of long noncoding RNAs (lncRNAs) in liver fibrosis is being increasingly recognized. However, the exact mechanisms and functions of the majority of lncRNAs are poorly characterized. In the present study, the hepatotoxic substance carbon tetrachloride (CCl(4)) was employed to induce liver fibrosis in an animal model and agenome-wide identification of lncRNAs in fibrotic liver tissues compared with CCl(4) untreated liver tissues was performed using RNA sequencing. Sprague-Dawley rats were treated with CCl(4) for 8 weeks. Histopathogical alterations were observed in liver tissues, and serum levels of alanine aminotransferase, aspartate aminotransferase, transforming growth factor-β1 and tumor necrosis factor-α were significantly higher, in the CCl(4)-treated group compared with the CCl(4) untreated group. RNA sequencing of liver tissues demonstrated that 231 lncRNAs and 1,036 mRNAs were differentially expressed between the two groups. Furthermore, bioinformatics analysis demonstrated that the differentially expressed mRNAs were predominantly enriched in ‘ECM-receptor interaction’, ‘PI3K-Akt signaling pathway’ and ‘focal adhesion’ pathways, all of which are essential for liver fibrosis development. Validation of 12 significantly aberrant lncRNAs by reverse transcription-quantitative polymerase chain reaction indicated that the expression patterns of 11 lncRNAs were consistent with the sequencing data. Furthermore, overexpression of lncRNA NR_002155.1, which was markedly downregulated in CCl(4)-treated liver tissues, was demonstrated to inhibit HSC-T6 cell proliferation in vitro. In conclusion, the present study determined the expression patterns of mRNAs and lncRNAs in fibrotic liver tissue induced by CCl(4). The identified differentially expressed lncRNAs may serve as novel diagnostic biomarkers and therapeutic targets for liver fibrosis.