title: Hotair facilitates hepatic stellate cells activation and fibrogenesis in the liver.
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.
authors.affiliation: School of pharmacy, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei 230032, China.
authors.forename: Er-Bao
authors.initials: EB
authors.lastname: Bian
authors.affiliation: School of pharmacy, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei 230032, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Wang
authors.affiliation: School of pharmacy, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei 230032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of pharmacy, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei 230032, China.
authors.forename: Bao-Ming
authors.initials: BM
authors.lastname: Wu
authors.affiliation: School of pharmacy, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei 230032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: School of pharmacy, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei 230032, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Meng
authors.affiliation: School of pharmacy, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei 230032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of pharmacy, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei 230032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of pharmacy, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei 230032, China.
authors.forename: Xiong-Wen
authors.initials: XW
authors.lastname: Lv
authors.affiliation: School of pharmacy, Anhui Medical University, Hefei 230032, China; Neuroscience Institute, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310-1945, USA. Electronic address: zxiong@msm.edu.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Xiong
authors.affiliation: School of pharmacy, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei 230032, China. Electronic address: lj@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D000076123:DNA (Cytosine-5-)-Methyltransferase 1 / Q000235:genetics; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C000608169:HOTAIR long non-coding RNA, mouse; C561566:HOTAIR long untranslated RNA, human; C498907:MEG3 non-coding RNA, human; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D000076123:DNA (Cytosine-5-)-Methyltransferase 1
keywords: Hepatic stellate cell (HSC); Hotair; Liver fibrosis; MEG3; PRC2