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circ_0103896/miR-432-5p/FTO feedback loop suppresses the formation and progression of intracranial aneurysm

Zhiwen Lu1, Shijie Zhu2, Yina Wu2

  • 1Department of Neurosurgery, Naval Medical Center, The PLA Naval Medical University, Shanghai, 200052, China.

Non-Coding RNA Research
|January 8, 2026
PubMed

Insights

Circular RNAs (circRNAs) and m6A RNA methylation regulate intracranial aneurysms (IA). We found circ_0103896 suppresses IA progression by interacting with miR-432-5p and FTO, offering a potential therapeutic target.

Area of Science:

  • Vascular Biology
  • Epigenetics
  • RNA Biology

Background:

  • Circular RNAs (circRNAs) and N6-methyladenosine (m6A) RNA methylation are implicated in intracranial aneurysm (IA) pathogenesis.
  • The specific interplay between circRNAs and m6A modification in IA remains largely unexplored.

Purpose of the Study:

  • To investigate the regulatory relationship between circRNAs and m6A RNA methylation in IA.
  • To identify specific circRNAs involved in IA progression and elucidate their underlying mechanisms.

Main Methods:

  • CircRNA profiling of IA tissues and control arteries.
  • RT-qPCR for gene expression analysis.
  • In vitro cell-based assays (hBVSMC phenotypic switch) and in vivo IA models.

Main Results:

  • hsa_circ_0103896 was significantly downregulated in IA tissues and correlated with IA progression.
  • circ_0103896 inhibited human brain vascular smooth muscle cell (hBVSMC) phenotypic switching and alleviated IA severity in vivo.
  • Mechanistically, circ_0103896 acted as a sponge for miR-432-5p, upregulating FTO and promoting circ_0103896 demethylation via an m6A feedback loop.

Conclusions:

  • The circ_0103896/miR-432-5p/FTO axis suppresses hBVSMC phenotypic transformation and mitigates IA progression.
  • This study reveals a novel epigenetic regulatory mechanism involving m6A modification and circRNA-miRNA crosstalk in IA.
  • circ_0103896 represents a potential therapeutic target for IA treatment.
Keywords:
Intracranial aneurysmPhenotypic transformationVascular smooth muscle cellscircRNAm6A modificationmicroRNA

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