Related Experiment Video

Updated: May 26, 2025

In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions
10:27

In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions

Published on: October 21, 2022

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Circ-Sirt6 promotes the stability and expression of m6A modified Sirt6 mRNA by recruiting IGF2BP2

Chuanfeng Zhang1, Jianing Wang1, Peng Kong2

  • 1Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, P.R. China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|February 21, 2025
PubMed

Insights

Circular RNA circ-Sirt6 is downregulated in coronary artery disease (CAD). Upregulating circ-Sirt6 inhibits vascular smooth muscle cell proliferation and migration, offering a potential new target for CAD treatment.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Epigenetics

Background:

  • Coronary artery disease (CAD) remains a leading global cause of mortality.
  • Circular RNAs (circRNAs) are increasingly recognized as regulators in CAD pathogenesis.
  • Further exploration of circRNA regulatory networks is crucial for understanding CAD progression.

Purpose of the Study:

  • To identify novel circRNA regulators involved in CAD.
  • To investigate the role of circ-Sirt6 in vascular smooth muscle cell (VSMC) proliferation and migration.
  • To elucidate the molecular mechanism underlying circ-Sirt6's function in CAD.

Main Methods:

  • Microarray analysis to identify differentially expressed circRNAs.
  • qRT-PCR to quantify circ-Sirt6 levels in VSMCs.
  • EdU incorporation and migration assays to assess VSMC proliferation and migration.
  • RNA pull-down, RIP, FISH, and immunofluorescence to confirm molecular interactions.
  • Dot blot and m6A-IP-qPCR to analyze m6A modification.

Main Results:

  • Circ-Sirt6 expression was significantly downregulated in VSMCs under pathological conditions (PDGF-BB treatment, balloon injury).
  • Overexpression of circ-Sirt6 suppressed in vitro and in vivo VSMC proliferation and migration.
  • Circ-Sirt6 binds to IGF2BP2, enhancing m6A modification of Sirt6 mRNA, thereby increasing its stability and expression.
  • Circ-Sirt6 plays a critical role in regulating VSMC phenotype switching via m6A modification.

Conclusions:

  • Circ-Sirt6 acts as a suppressor of VSMC proliferation and migration.
  • The circ-Sirt6/IGF2BP2/Sirt6 axis, mediated by m6A modification, is a key regulatory pathway in CAD.
  • Circ-Sirt6 represents a promising therapeutic target for CAD intervention.

Keywords:
IGF2BP2Sirt6 mRNAVSMCscirc‐Sirt6m6A

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