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

Sep 29, 2026

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Circular RNAs (circRNAs) and m6A RNA methylation contribute to intracranial aneurysm (IA), yet their coordinated regulation is unclear. Using circRNA profiling of 16 IA tissues and 8 superficial temporal arteries, hsa_circ_0103896 was identified as markedly downregulated. Reduced circ_0103896 or elevated miR-432-5p tracked with IA progression, while circ_0103896 modulated human brain vascular smooth muscle cell phenotypic switching and influenced aneurysm severity in vivo. Mechanistically, circ_0103896 sponges miR-432-5p to upregulate FTO, promoting m6A demethylation of circ_0103896 and forming a positive feedback loop. The circ_0103896/miR-432-5p/FTO axis suppresses phenotypic transformation and mitigates IA progression.

LanguageEnglish

CategoryResearch & Report

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Pages17

Reading Time43 min

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Introduction

Vascular smooth muscle cells and phenotypic switching in intracranial aneurysm

Noncoding RNAs, circRNAs, and miRNAs in IA regulation

Non-coding RNA Research 17 (2026) 59–75 Contents lists available at ScienceDirect Non-coding RNA Research journal [homepage:](homepage: www.keaipublishing.com/en/journals/non-coding-rna-research)[ www.keaipublishing.com/en/journals/non-coding-rna-research](homepage: www.keaipublishing.com/en/journals/non-coding-rna-research) | Original Research Article
circ_ 0103896/miR-432–5p/FTO feedback loop suppresses the formation and progression of intracranial aneurysm | | | | | --- | --- | --- | --- | | Zhiwen Lua,1, Shijie Zhub,1, Yina Wub, Fengfeng Xu a, Qinghai Huang c,*
a Department of Neurosurgery, Naval Medical Center, The PLA Naval Medical University, Shanghai, 200052, China b Department of Neurovascular Centre, Changhai Hospital, Naval Medical University, Shanghai, 200433, China c Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, China | | | | | A R T I C L E I N F O | | A B S T R A C T | | | Keywords:
Intracranial aneurysm circRNA
microRNA
m6A modification
Vascular smooth muscle cells Phenotypic transformation | | Circular RNAs (circRNAs) and m6A RNA methylation play crucial roles in the pathogenesis of intracranial aneurysm (IA); however, their regulatory interplay remains unclear. Through circRNA profiling of 16 IA tissues and 8 superficial temporal arteries, we identified hsa_circ_0103896 as significantly downregulated in IA. RTqPCR analysis further revealed that decreased circ_0103896 or increased miR-432–5p expression correlated with IA progression. Functional assays demonstrated that circ_0103896 inhibited the phenotypic switch of human brain vascular smooth muscle cells (hBVSMCs) from a contractile to a synthetic state, whereas circ_0103896 knockdown reversed this effect. In vivo, circ_0103896 overexpression alleviated IA severity, whereas its depletion aggravated aneurysm formation. Mechanistically, circ_0103896 functioned as a sponge for miR-432–5p, thereby upregulating FTO, which in turn promoted m6A demethylation of circ_0103896. This process reinforced circ_0103896 expression, forming a positive feedback loop. The circ_ 0103896/miR-432–5p/ FTO axis thus suppresses hBVSMC phenotypic transformation and mitigates IA progression. These findings reveal a novel epigenetic mechanism involving m6A modification and circRNA–miRNA crosstalk in IA pathogenesis, highlighting circ_0103896 as a potential therapeutic target. | | 1. Introduction Intracranial aneurysms (IAs) are pathological dilations of cerebral arteries that pose a substantial risk of rupture and life-threatening subarachnoid hemorrhage [1]. Although the exact mechanisms underlying IA formation and rupture remain incompletely understood, current evidence suggests that vascular wall pathology, driven by endothelial dysfunction, extracellular matrix remodeling, and phenotypic modulation of vascular smooth muscle cells (VSMCs), plays a pivotal role in their pathogenesis [2]. VSMCs play a crucial role in maintaining vascular integrity and are implicated in various cerebrovascular disorders, including IA [3]. These highly specialized contractile cells are primarily responsible for preserving vascular morphology and regulating blood pressure [4]. Accumulating evidence indicates that VSMCs possess remarkable plasticity, enabling them to undergo profound phenotypic changes in response to diverse environmental stimuli [5,6]. This adaptability facilitates their transition from a contractile to a synthetic phenotype, a process known as phenotypic switching. The synthetic phenotype is characterized by downregulated expression of contractile markers, such as smooth muscle protein 22α (SM22α) and α-smooth muscle actin (α-SMA), accompanied by upregulated production of inflammatory mediators, including tumor necrosis factor-α (TNF-α) and matrix metalloproteinases (MMPs) [7]. These proinflammatory and matrix-degrading properties of synthetic VSMCs contribute to extracellular matrix remodeling and medial l

FAQs

What role does circ_0103896 play in intracranial aneurysm progression?

circ_0103896 expression is significantly reduced in IA. Functional and in vivo results show that decreasing circ_0103896 worsens aneurysm formation and severity, while overexpression alleviates progression.

How does miR-432-5p relate to circ_0103896 and IA?

In the study, increased miR-432-5p expression correlates with IA progression. Mechanistically, circ_0103896 acts as a sponge for miR-432-5p, linking their regulation to downstream effects.

What is the mechanistic pathway involving FTO and m6A modification?

circ_0103896 sponges miR-432-5p to upregulate FTO. FTO then promotes m6A demethylation of circ_0103896, reinforcing circ_0103896 expression and creating a positive feedback loop that suppresses IA-associated phenotypic transformation.

Sep 29, 2026

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