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MAPK Is a Mutual Pathway Targeted by Anxiety-Related miRNAs, and E2F5 Is a Putative Target for Anxiolytic miRNAs

Javad Amini1, Cordian Beyer2, Adib Zendedel2,3

  • 1Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd 94149-75516, Iran.

Biomolecules
|March 29, 2023
PubMed

Insights

Anxiety-related microRNAs (miRs) were identified, with specific anxiolytic and anxiogenic miRs targeting key genes. These miRs, particularly through the MAPK pathway, influence anxiety pathophysiology, highlighting E2F5 as a potential target.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Anxiety-related disorders (ARDs) are a leading cause of global disability.
  • MicroRNA (miR) dysregulation is implicated in neuropsychiatric disorders.

Purpose of the Study:

  • To identify specific microRNAs (miRs) involved in anxiety processing in the brain.
  • To elucidate the target genes and cellular pathways influenced by these anxiety-related miRs (ARmiRs).

Main Methods:

  • Collection of experimentally confirmed ARmiRs.
  • Prediction of ARmiR target transcripts.
  • Identification of critical cellular pathways and hub genes.

Main Results:

  • Nine anxiolytic and ten anxiogenic ARmiRs were identified.
  • Anxiolytic miRs target genes like Acsl4, Aff4, and Klf4; anxiogenic miRs target other genes.
  • The MAPK signaling pathway is significantly affected by both anxiolytic and anxiogenic miRs.

Conclusions:

  • Key anxiolytic (e.g., miR-34c) and anxiogenic (e.g., miR-19b) miRs act as epigenetic modulators in anxiety pathophysiology.
  • The MAPK signaling pathway is a primary mediator of miR influence on anxiety.
  • E2F5 emerges as a novel putative target for anxiolytic miRs in ARDs.
Keywords:
anxietydepressionepigeneticmiRNAsnon-coding RNAs

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