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Roquin Modulates Cardiac Post-Infarct Remodeling via microRNA Stability Control.

Nadja Itani1, Rolf Schreckenberg1, Rainer Schulz1

  • 1Physiologisches Institut, Justus-Liebig-Universität Gießen, 35392 Gießen, Germany.

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|November 26, 2025
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Summary

Hypoxia down-regulates Roquin proteins, increasing microRNA-23b-5p stability. This Roquin-2-dependent microRNA then silences the ZBTB20 transcription factor, impacting heart recovery after ischemia.

Keywords:
ZBTB20miR-23b-5ppost-infarct remodeling

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Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Gene Regulation

Background:

  • MicroRNAs (miRNAs) regulate gene expression by binding to complementary mRNAs.
  • The RNA-binding proteins Roquin-1 and Roquin-2 control miRNA stability and half-life.
  • Understanding Roquin's role in miRNA-dependent gene regulation is crucial for post-ischemic heart conditions.

Purpose of the Study:

  • To investigate the function of Roquin in the miRNA-dependent regulation of the transcriptome in the post-ischemic heart.
  • To identify specific miRNAs and their targets involved in this process.

Main Methods:

  • Integrative miRNA-and-mRNA analysis (MMIA) was employed.
  • Expression levels of Roquin isoforms, miR-23b-5p, and ZBTB20 were analyzed under various conditions (hypoxia, normoxia, siRNA knockdown, antagomir treatment).
  • Correlation analysis between ZBTB20 expression and heart functional recovery was performed.

Main Results:

  • Hypoxia down-regulates both Roquin-1 and Roquin-2 in cardiomyocytes.
  • miR-23b-5p was identified as a Roquin interaction partner, and ZBTB20 as its target.
  • Roquin-2 knockdown increased miR-23b-5p and decreased ZBTB20 levels.
  • Hypoxia-induced ZBTB20 down-regulation was reversed by inhibiting miR-23b-5p.
  • ZBTB20 expression correlated with rat heart recovery post-myocardial infarction.

Conclusions:

  • Hypoxia-induced Roquin down-regulation leads to increased stability of Roquin-2-dependent miR-23b-5p.
  • This results in the silencing of the transcription factor ZBTB20.
  • The Roquin-miR-23b-5p-ZBTB20 axis plays a significant role in the post-ischemic heart's response and recovery.