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Deregulation of exosomal miRNAs in rheumatoid arthritis patients

Muhammad Zahid Hussain1, Muhammad Shahbaz Haris2, Muhammad Rizwan2

  • 1Department of Rheumatology, National University of Medical Sciences, Rawalpindi, Pakistan.

Plos One
|July 27, 2023
PubMed

Insights

Exosomal microRNAs (miRNAs) are significantly downregulated in rheumatoid arthritis (RA) patients, correlating with increased oxidative stress and histone deacetylation. These deregulated miRNAs show potential as biomarkers for RA pathogenesis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Immunology

Background:

  • Exosomes mediate intercellular communication via their cargo, including microRNAs (miRNAs).
  • Dysregulated miRNAs contribute to disease pathogenesis by altering protein output.
  • Limited research exists on exosomal miRNAs in rheumatoid arthritis (RA) pathogenesis.

Purpose of the Study:

  • To investigate the role of specific exosomal miRNAs (miRNA-103a-3p, miRNA-10a-5p, miRNA-204-3p, miRNA-330-3p, and miRNA-19b) in RA pathogenesis.
  • To explore the association of these exosomal miRNAs with oxidative stress and histone deacetylation in RA patients.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) to assess exosomal miRNA expression levels in 306 RA patients and controls.
  • Enzyme-linked immunosorbent assay (ELISA) to measure 8-hydroxydeoxyguanosine (8-OHdG) for oxidative stress and histone deacetylation levels.
  • Statistical analyses including correlation and Receiver Operating Characteristics (ROC) curve analysis.

Main Results:

  • Significantly downregulated expression of all five investigated exosomal miRNAs in RA patients compared to controls (p<0.0001).
  • Significantly increased levels of oxidative stress (8-OHdG) and histone deacetylation in RA patients (p<0.0001).
  • Negative correlation observed between deregulated exosomal miRNAs and increased oxidative stress/histone deacetylation.
  • ROC analysis indicated good diagnostic potential for these miRNAs in RA.

Conclusions:

  • The study identifies a significant downregulation of specific exosomal miRNAs in RA patients.
  • Deregulated exosomal miRNAs are linked to increased oxidative stress and histone deacetylation in RA.
  • These exosomal miRNAs may play a role in RA initiation and progression, potentially serving as diagnostic biomarkers.

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