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Updated: Oct 2, 2025

Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
The Combined Effects of Circular RNA Methylation Promote Pulmonary Fibrosis
Sha Wang1,2,3,4, Wei Luo1,2,3,4, Jie Huang1,2
1Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Abstract:
m6A (N6-methyladenosine) is the most common type of RNA methylation modification, mainly occurring on mRNA. Whether m6A-modified circular RNAs (circRNAs) are involved in pulmonary fibrosis in different settings remains unclear. Using an m6A-circRNA epitranscriptomic chip, candidate circRNAs were selected, among which hsa_circ_0000672 and hsa_circ_0005654 were specifically involved in SiO2-induced pulmonary fibrosis by targeting the same protein, eIF4A3, indicating that the m6A modification of these two circRNAs has a synergistic effect on fibroblast dysfunction induced by SiO2. A mechanistic study revealed that the m6A modification of circRNAs was mainly mediated by the methyltransferase METTL3. Furthermore, METTL3 promoted the activation, migration, and activity of pulmonary fibroblasts and participated in SiO2-induced pulmonary fibrosis via the circRNA m6A modification. m6A methylation of circRNAs mediates silica-induced fibrosis, enriching the understanding of circRNAs and uncovering a potential new target for treating fibrosis-related diseases.
Insights
N6-methyladenosine (m6A) modification of circular RNAs (circRNAs) plays a key role in silica-induced pulmonary fibrosis. METTL3-mediated m6A circRNAs synergistically promote fibroblast dysfunction, offering potential therapeutic targets for fibrosis.
Area of Science:
- Epitranscriptomics
- Molecular Biology
- Pulmonary Medicine
Background:
- N6-methyladenosine (m6A) is the most prevalent RNA modification, primarily on mRNA.
- The role of m6A-modified circular RNAs (circRNAs) in pulmonary fibrosis is not well understood.
Purpose of the Study:
- To investigate the involvement of m6A-modified circRNAs in silica-induced pulmonary fibrosis.
- To elucidate the underlying molecular mechanisms and identify potential therapeutic targets.
Main Methods:
- Utilized an m6A-circRNA epitranscriptomic chip to identify candidate circRNAs.
- Conducted mechanistic studies to explore the role of METTL3 and specific circRNAs (hsa_circ_0000672, hsa_circ_0005654) in fibroblast function.
- Investigated the interaction with eIF4A3.
Main Results:
- Identified hsa_circ_0000672 and hsa_circ_0005654 as key players in SiO2-induced pulmonary fibrosis.
- Demonstrated that m6A modification of these circRNAs synergistically impairs fibroblast function via eIF4A3.
- Revealed that METTL3 mediates circRNA m6A modification, promoting fibroblast activation, migration, and activity in silica-induced fibrosis.
Conclusions:
- m6A methylation of circRNAs is a critical mediator of silica-induced pulmonary fibrosis.
- METTL3-driven m6A circRNA modification contributes to fibroblast dysfunction.
- These findings highlight circRNA m6A modification as a potential therapeutic strategy for treating fibrotic diseases.
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