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Long non-coding RNA XIST binding to let-7c-5p contributes to rheumatoid arthritis through its effects on

Zong-Qiang Wang1, Dian-Hui Xiu2, Jin-Lan Jiang3,4

  • 1Medical Department, China-Japan Union Hospital of Jilin University, Changchun, China.

Journal of Clinical Laboratory Analysis
|September 4, 2020
PubMed
Abstract

Insights

Downregulating long non-coding RNA XIST (lncRNA XIST) in rheumatoid arthritis (RA) promotes osteoblast function and reduces inflammation. This suggests lncRNA XIST is a potential therapeutic target for RA treatment.

Area of Science:

  • Molecular Biology
  • Immunology
  • Rheumatology

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease impacting 1% of the global population, significantly reducing patient quality of life.
  • This study investigates the role of long non-coding RNA XIST (lncRNA XIST) in RA pathogenesis.
  • The research explores the underlying mechanisms involving let-7c-5p and signal transducer and activator of transcription 3 (STAT3).

Purpose of the Study:

  • To explore the role of lncRNA XIST in rheumatoid arthritis (RA).
  • To elucidate the mechanisms of lncRNA XIST involving let-7c-5p and STAT3 in RA.
  • To evaluate lncRNA XIST as a potential therapeutic target for RA.

Main Methods:

  • Assessed lncRNA XIST, let-7c-5p, and STAT3 expression in RA and normal cartilage tissues.
  • Analyzed the relationship between these molecules in osteoblasts.
  • Investigated the regulatory effects of XIST modulation (upregulation/downregulation) in osteoblasts.
  • Measured inflammatory markers (TNF-α, IL-2, IL-6) and bone markers (ALP, osteocalcin, TGF-β1, IGF1) in vivo in RA rat models.

Main Results:

  • High expression of lncRNA XIST and STAT3, and low expression of let-7c-5p were observed in RA cartilage.
  • Silencing lncRNA XIST or enhancing let-7c-5p reduced inflammatory markers (TNF-α, IL-2, IL-6).
  • These modulations increased bone formation markers (ALP, osteocalcin, TGF-β1, IGF-1) and decreased cartilage damage.

Conclusions:

  • Downregulation of lncRNA XIST promotes osteoblast proliferation and differentiation in RA.
  • lncRNA XIST serves as a potential therapeutic target for rheumatoid arthritis.
  • The interplay between lncRNA XIST, let-7c-5p, and STAT3 is crucial in RA progression.
Keywords:
Let-7c-5plong non-coding RNA X-inactive specific transcriptosteoblastrheumatoid arthritissignal transducer and activator of transcription 3

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