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Target intelligence / Profile preview
Thrombospondin 1 antisense RNA 1 (THBS1-AS1)
- Target
- THBS1-AS1
- Molecular classification
- Long noncoding RNA (lncRNA), Other
01
Overview
Thrombospondin 1 antisense RNA 1 (THBS1-AS1) is a long noncoding RNA transcribed from the antisense strand of the THBS1 locus and has been implicated as a regulator of cardiac fibrosis[3][4]. It is upregulated in cardiac fibroblasts in response to TGF-β1 stimulation, promoting fibroblast activation, proliferation, migration, extracellular matrix deposition, and fibrogenic gene expression via upregulation of TGF-β receptor 1 (TGFBR1)[3][4]. Mechanistically, THBS1-AS1 acts as a molecular sponge for miR-221/222, thereby releasing repression of TGFBR1 and amplifying TGF-β pathway signaling. Knockdown experiments in mouse and human models show that inhibition of THBS1-AS1 reduces cardiac fibroblast activation and fibrosis[4]. THBS1-AS1 is under transcriptional control of the transcription factor Meox1. It is considered a novel therapeutic target for the treatment and prevention of cardiac fibrosis, with translational relevance to human cardiac disease[3][4].
- Other names
- THBS1-AS1thrombospondin 1 antisense 1ENST00000616754.1 (human transcript)ENSG00000278621 (human gene)lncRNA-THBS1-AS1
02
Mechanism of action
Sponging miR-221/222 to regulate TGFBR1 expression; Modulation of TGF-β1-mediated fibroblast activation
03
Biological functions
Regulation of cardiac fibroblast activationModulation of TGF-β signaling pathwayRegulation of cell proliferationRegulation of fibrosisSponging of microRNAs (miR-221/222)Regulation of gene expression (TGFBR1)
04
Disease associations
Cardiovascular diseaseFibrosis (specifically cardiac fibrosis)
05
Safety considerations
No specific safety concerns reported; knockdown strategies appear to reduce cardiac fibrosis without major side effects in animal models[4]
06
Biomarkers
THBS1-AS1 levels as a potential biomarker for cardiac fibroblast activation and cardiac fibrosis[4]Expression changes in TGFBR1, POSTN, CTGF, α-SMA as downstream readouts of THBS1-AS1 modulation[4]
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