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Updated: Mar 22, 2026

A Deep-sequencing-assisted, Spontaneous Suppressor Screen in the Fission Yeast Schizosaccharomyces pombe
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circFAM53B-1 and circFAM53B-2 drive VSMC phenotypic modulation via ISG15-mediated suppression of SRF

Lingdan Zhao1, Yan Li1, Ran Bi1

  • 1Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China.

Cellular Signalling
|March 20, 2026
PubMed

Insights

Two novel circRNAs, circFAM53B-1 and circFAM53B-2, regulate vascular smooth muscle cell (VSMC) switching by controlling ISG15 and SRF. This reveals new mechanisms in vascular remodeling.

Area of Science:

  • Vascular Biology
  • Molecular Biology
  • Epigenetics

Background:

  • Vascular smooth muscle cells (VSMCs) phenotypic modulation is crucial in vascular diseases.
  • The role of circular RNAs (circRNAs) in VSMC regulation is not fully understood.
  • Identifying novel regulatory mechanisms is essential for understanding vascular remodeling.

Purpose of the Study:

  • To investigate the function of circFAM53B-1 and circFAM53B-2 in VSMC phenotypic switching.
  • To elucidate the molecular mechanisms underlying circRNA-mediated VSMC regulation.
  • To explore potential therapeutic targets for vascular diseases.

Main Methods:

  • Upregulation of circFAM53B-1 and circFAM53B-2 by PDGF-BB.
  • KLF4-dependent regulation of circRNA expression.
  • Assessment of VSMC contractile markers (α-SMA, SM22α) and SRF levels.
  • Investigation of the ISG15-SRF pathway and ubiquitin-proteasome degradation.

Main Results:

  • PDGF-BB upregulates circFAM53B-1 and circFAM53B-2 via KLF4.
  • These circRNAs decrease VSMC contractile markers by suppressing SRF.
  • The PDGF-BB-KLF4-circFAM53B1/2 axis enhances ISG15, promoting SRF degradation and VSMC switching.
  • circFAM53B-1 and circFAM53B-2 are key regulators via the ISG15-SRF pathway.

Conclusions:

  • circFAM53B-1 and circFAM53B-2 are novel regulators of VSMC phenotypic switching.
  • The ISG15-SRF pathway is a key mechanism in circRNA-mediated VSMC modulation.
  • These findings offer insights into vascular remodeling and potential therapeutic strategies.
Keywords:
ISG15KLF4VSMCs phenotype switchingcircFAM53B-1/2

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