Genome‑wide identification of long noncoding RNAs in CCl4‑induced liver fibrosis via RNA sequencing

Gong,Zhenghua; Tang,Jialin; Xiang,Tianxin; Lin,Jiayu; Deng,Chaowen; Peng,Yanzhong; Zheng,Jie; Hu,Guoxin

doi:10.3892/mmr.2018.8986

Genome‑wide identification of long noncoding RNAs in CCl4‑induced liver fibrosis via RNA sequencing

Authors:
- Zhenghua Gong
- Jialin Tang
- Tianxin Xiang
- Jiayu Lin
- Chaowen Deng
- Yanzhong Peng
- Jie Zheng
- Guoxin Hu
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Affiliations: Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China, Department of Public Health, Center for Disease Control and Prevention in Jiangxi, Nanchang, Jiangxi 330029, P.R. China, Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Digestive Diseases, The Eighth Affiliated Hospital of Sun Yat‑sen University, Shenzhen, Guangdong 518033, P.R. China, Department of Infectious Diseases, Peking University Shenzhen Hospital, Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China, Department of Traditional Chinese Medicine, Peking University Shenzhen Hospital, Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China
Published online on: May 7, 2018 https://doi.org/10.3892/mmr.2018.8986
Pages: 299-307
Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 (CCl4) was employed to induce liver fibrosis in an animal model and agenome‑wide identification of lncRNAs in fibrotic liver tissues compared with CCl4 untreated liver tissues was performed using RNA sequencing. Sprague‑Dawley rats were treated with CCl4 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 CCl4‑treated group compared with the CCl4 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 ʻECM‑receptor interactionʼ, ʻPI3K‑Akt signaling pathwayʼ and ʻfocal adhesionʼ 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 CCl4‑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 CCl4. The identified differentially expressed lncRNAs may serve as novel diagnostic biomarkers and therapeutic targets for liver fibrosis.

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