MicroRNA-7188-5p and miR-7235 regulates Multiple sclerosis in an experimental mouse model

Hairul-Islam Mohamed Ibrahim1, Abdullah AlZahrani2, Hamza Hanieh3

  • 1Biological Sciences Department, College of Science, King Faisal University, Hofouf, Alhasa, 31982, Saudi Arabia; Pondicherry Centre for Biological Science and Educational Trust, Pondicherry, 605005, India.

Molecular Immunology
|September 20, 2021
PubMed

Insights

Researchers identified novel microRNAs (miRNAs) and their mRNA targets implicated in Multiple Sclerosis (MS). Specific miRNAs, like miR-7188-5p and miR-7235, showed therapeutic potential by alleviating disease symptoms in experimental models.

Area of Science:

  • Neuroscience
  • Genetics
  • Immunology

Background:

  • MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and are implicated in various pathological conditions, including autoimmune diseases.
  • Multiple Sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system, with complex underlying molecular mechanisms that are not fully understood.

Purpose of the Study:

  • To identify novel differentially expressed miRNAs and their downstream mRNA targets in Multiple Sclerosis (MS).
  • To investigate the potential therapeutic and prognostic applications of identified miRNAs in MS.

Main Methods:

  • Computational tools were used for preliminary in silico screening to identify differentially expressed miRNAs in EAE mice models.
  • In vivo and in vitro experiments, including mimic and silencing miRNA models, were conducted to validate miRNA targets and their roles.
  • Adoptive transfer models were employed to assess the in vivo effects of specific miRNAs on disease progression and central nervous system (CNS) pathophysiology.

Main Results:

  • A set of miRNAs, including miR-659-3p, miR-659-5p, miR-684, miR-3607, miR-3682, miR-4647, miR-7188, and miR-7235, were found to be elevated in the secondary lymphoid cells of EAE mice.
  • Reciprocal expression patterns were observed between these miRNAs and their downstream target mRNAs (e.g., FXBO33, SGMS-1, ZDHHC-9, GABRA-3, NRXN-2) in lymphoid cells.
  • Suppression of miR-7188-5p and miR-7235 in vivo altered astrocyte patterns and CNS pathophysiology, leading to enhanced disease alleviation in experimental MS models.

Conclusions:

  • The study identified a novel set of miRNAs and their mRNA targets implicated in the pathogenesis of MS.
  • Specific miRNAs, particularly miR-7188-5p and miR-7235, demonstrate significant therapeutic potential for experimental MS.
  • These findings highlight promising miRNA biomarkers for therapeutic intervention and further research in MS.

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