Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5501137 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2017 | 43 Pages |
Abstract
Long non-coding RNAs (lncRNAs) are increasingly recognized as major players in regulating various biological processes. LncRNA HOX transcript antisense RNA (Hotair) has been extensively studied in cancer. However, the role of Hotair in liver fibrosis remains unknown. Here we observed that Hotair expression was significantly increased in CCl4-induced mouse liver fibrosis models, human fibrotic livers and activated hepatic stellate cells (HSCs) by TGF-β1 stimulation. Enforced expression of Hotair in LX-2 cells promoted cell proliferation and activation while inhibition of its expression had an opposite effect. Furthermore, we found that Hotair may act as an endogenous 'sponge' of miR-148b, which regulates expression of the DNMT1/MEG3/p53 pathways in HSCs. Intriguingly, Hotair enhanced polycomb repressive complex 2 (PRC2) occupancy and histone H3K27me3 repressive marks, specifically at the MEG3 promoter region. Finally, we found that Hotair forms an RNA/DNA hybrid and recruits PRC2 to MEG3 promoter. These data suggest that Hotair inhibition may represent a promising therapeutic option for suppressing liver fibrosis.
Keywords
α-SMADNA methyltransferase 1HULCPRC2H3K27me3COL1A1ncRNAHSCsDZNepEZH2Dnmt1MEG3MMP-2TLSmiRNAsH&EHCCNon-coding RNAcompeting endogenous RNAsalpha smooth muscle actintranslocated in liposarcomamicroRNAsceRNAsHepatic stellate cellsLiver fibrosishaematoxylin and eosinHOTAIRpolycomb repressive complex 2maternally expressed gene 3Hepatocellular carcinoma
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Authors
Er-Bao Bian, Yuan-Yuan Wang, Yang Yang, Bao-Ming Wu, Tao Xu, Xiao-Ming Meng, Cheng Huang, Lei Zhang, Xiong-Wen Lv, Zhi-Gang Xiong, Jun Li,