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miR-125b and miR-223 Contribute to Inflammation by Targeting the Key Molecules of NFκB Pathway

Swati Valmiki1, Vineet Ahuja2, Niti Puri1

  • 1School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.

Frontiers in Medicine
|February 11, 2020
PubMed

Insights

MicroRNAs miR-125b and miR-223 are upregulated in ulcerative colitis (UC) and target inflammatory pathway genes TRAF6, A20, and IKKα. These miRNAs may serve as biomarkers for UC diagnosis.

Area of Science:

  • Gastroenterology and Molecular Biology
  • Inflammation and Immunology

Background:

  • Ulcerative colitis (UC) pathogenesis involves complex inflammatory pathways.
  • MicroRNAs (miRNAs) are increasingly recognized for their role in inflammatory diseases.
  • Differential expression of specific miRNAs, like miR-125b and miR-223, is observed in UC patients.

Purpose of the Study:

  • To investigate the biological relevance of altered miR-125b and miR-223 expression in UC.
  • To identify potential gene targets of miR-125b and miR-223 involved in UC pathogenesis.
  • To validate the regulatory role of these miRNAs in inflammatory pathways.

Main Methods:

  • Identification of potential gene targets for miR-125b (TRAF6, A20) and miR-223 (IKKα) using bioinformatics or literature review.
  • Quantification of miRNA and target gene expression in colonic mucosal samples from UC patients.
  • In vitro validation using co-transfection experiments in HT29 cells.
  • Assessment of inflammatory markers (p65, IL-8, IL-1β) following miRNA co-transfection and lipopolysaccharide (LPS) stimulation.

Main Results:

  • UC patients showed significantly increased miR-125b and miR-223 expression.
  • A corresponding downregulation of target genes TRAF6, A20, and IKKα was observed in UC patients.
  • Co-transfection experiments confirmed the negative regulatory effect of miR-125b on TRAF6/A20 and miR-223 on IKKα.
  • Overexpression of miR-125b or miR-223 in HT29 cells led to increased p65 and pro-inflammatory cytokine (IL-8, IL-1β) expression upon LPS stimulation.

Conclusions:

  • miR-125b and miR-223 contribute to the inflammatory response in UC by negatively regulating TRAF6, A20, and IKKα.
  • These miRNAs play a role in modulating the NFκB signaling pathway.
  • miR-125b and miR-223 are potential biomarkers for the screening and diagnosis of ulcerative colitis.
Keywords:
A20IKKαNFκB pathwayTRAF6inflammationmicroRNAulcerative colitis

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