Linc‐SCRG1 accelerates liver fibrosis by decreasing RNA‐binding protein tristetraprolin. Issue 2 (18th September 2018)

• Record Type: Journal Article
• Authors: Wu, Jun-Cheng; Luo, Sheng-Zheng; Liu, Ting; Lu, Lun-Gen; Xu, Ming-Yi
• Is Part Of: FASEB journal. Volume 33:Issue 2(2019)
• Page Start: 2105
• Page End: 2115
• Publication Date: 2018-09-18
• Subjects: long noncoding RNA -- hepatic stellate cell -- TTP; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201800098RR
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: The biologic roles of long noncoding RNAs (lncRNAs) in liver fibrosis remained unknown. Through microarray analysis, linc‐SCRG1 (a lncRNA with transcript length 3118 bp) was found up‐regulated 13.62‐fold in human cirrhotic tissues. Quantitative PCR verified that linc‐SCRG1 increased along with liver fibrosis progression in human tissues and in activated LX2 cells induced by TGF‐β1. Knockdown of linc‐SCRG1 significantly reversed the effects of TGF‐β1 on LX2, including inhibiting activation, promoting apoptosis, reducing proliferation, lessening invasion, and down‐regulating genes [fibrosis‐related mRNA: α‐smooth muscle actin (α ‐SMA ), type I collagen, and B‐cell lymρhoma‐2; invasion‐related mRNA: matrix metalloρeρtidase‐2 ( MMP‐2 ), MMP‐9, and MMP‐13 ; inflammation‐related mRNA: TNF‐ α, IL‐6, and IL‐10 ]. linc‐SCRG1 had binding sites with tristetraprolin (TTP), a kind of RNA‐binding protein, and specifically combined to TTP proteins. Overexpression of linc‐SCRG1 would cause TTP mRNA unstably and proteins decreasing. TTP mRNA was proved having negative relevance with linc‐SCRG1 and was gradually reduced during human liver fibrosis progression. Overexpressing TTP resulted in knockdown of lincSCRG1 and degraded downstream target genes ( MMP‐2 and TNF‐ α) in activated LX2. Overexpressing TTP had the same effects as small interfering RNA‐lincSCRG1 (si ‐lincSCRG1 ), whereas knockdown of TTP had reversal effects on si‐ lincSCRG1 in activated LX2. In summary, linc‐SCRG1 reduced TTP and restricted its degradation of target genes TNF‐α and MMP‐2 . Therefore, linc‐SCRG1 had a repressing TTP‐elicited inactivation effect on hepatic stellate cell (HSC) phenotypes. Inhibition of linc‐SCRG1 may be a novel therapeutic approach to inactivate HSCs and extenuate human liver fibrosis.—Wu, J.‐C., Luo, S.‐Z., Liu, T., Lu, L.‐G., Xu, M.‐Y. linc‐SCRG1 accelerates liver fibrosis by decreasing RNA‐binding protein tristetraprolin. FASEB J. 33, 2105–2115 (2019). www.fasebj.org