Format

Send to

Choose Destination
Biochim Biophys Acta Mol Basis Dis. 2017 Mar;1863(3):674-686. doi: 10.1016/j.bbadis.2016.12.009. Epub 2016 Dec 13.

Hotair facilitates hepatic stellate cells activation and fibrogenesis in the liver.

Author information

1
School of pharmacy, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei 230032, China.
2
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.
3
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.

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:

Hepatic stellate cell (HSC); Hotair; Liver fibrosis; MEG3; PRC2

PMID:
27979710
DOI:
10.1016/j.bbadis.2016.12.009
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center