Related Experiment Video
Updated: Jan 12, 2026
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
m6A Methylation-Modified hsa_circ_0044226 Attenuates Pulmonary Fibrosis by Suppressing Ferroptosis
Fei Qi1, Liwei Liu2, Cheng Peng3
1School of Clinical Medicine Anhui Institute of Medicine Hefei City Anhui Province People's Republic of China.
Abstract:
Idiopathic Pulmonary fibrosis (IPF) is a debilitating lung condition marked by chronic progression and reduced lung function. This study aimed to explore the functional role and regulatory mechanism of circular RNA circ_0044226 in the pathogenesis of pulmonary fibrosis. The expression of circ_0044226 was analyzed in peripheral blood and TGF-β1-stimulated RLE-6TN cells using qRT-PCR. The cellular location of circ_0044226 was analyzed using FISH. The expression levels of circ_0044226 and METTL3 were evaluated in cells and clinical samples. Protein levels of GPX4 and FTH1 were examined using Western blot, while the levels of MDA, Fe2+ and ROS were determined using commercial kits. The association of circ_0044226 with m6A modifications was validated by Methylated-RNA immunoprecipitation assay (MeRIP), RNA pulldown, RIP and dot blot assay. Finally, a Bleomycin (BLM) treated rat model was also utilized to verify the function of circ_0044226 in pulmonary fibrosis. The primary localization of circ_0044226 was within the cytoplasm and was found to be upregulated in blood samples from IPF patients and TGF-β1-treated RLE-6TN cells. Knockdown of circ_0044226 reduced the accumulation of free iron and MDA, and suppressed α-SMA and FN1 in TGF-β1-induced cells. Furthermore, METTL3 mediated the m6A modification of circ_0044226. Downregulation of METTL3 mitigated ferroptosis by inhibiting hsa_circ_0044226. The rat pulmonary fibrosis model further demonstrated that METTL3 knockdown alleviated pulmonary fibrosis by blocking ferroptosis through circ_0044226. Our findings demonstrated that targeting the METTL3/circ_0044226 axis attenuated pulmonary fibrosis by inhibiting ferroptosis in the studied models.
Insights
This study reveals that targeting the METTL3/circ_0044226 pathway can reduce pulmonary fibrosis. By inhibiting ferroptosis, this mechanism offers a new therapeutic strategy for idiopathic pulmonary fibrosis (IPF).
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Idiopathic Pulmonary Fibrosis (IPF) is a progressive lung disease characterized by declining lung function.
- Circular RNAs (circRNAs) are emerging as key players in various disease pathologies, including fibrosis.
- Understanding the regulatory mechanisms of circRNAs in IPF is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the functional role of circ_0044226 in the pathogenesis of pulmonary fibrosis.
- To elucidate the regulatory mechanism of circ_0044226, focusing on its interaction with METTL3 and its impact on ferroptosis.
- To validate the therapeutic potential of targeting the METTL3/circ_0044226 axis in preclinical models of pulmonary fibrosis.
Main Methods:
- Quantitative Real-Time PCR (qRT-PCR) and Fluorescence In Situ Hybridization (FISH) to analyze circ_0044226 expression and localization.
- Western blot and commercial kits to assess protein levels and markers of oxidative stress and iron accumulation.
- Methylated-RNA immunoprecipitation (MeRIP), RNA pulldown, and RIP assays to investigate m6A modification and interactions.
- Bleomycin (BLM)-induced rat model to evaluate the in vivo efficacy of targeting the METTL3/circ_0044226 axis.
Main Results:
- Circ_0044226 was upregulated in IPF patients and TGF-β1-stimulated cells, localized in the cytoplasm.
- Knockdown of circ_0044226 reduced iron accumulation, MDA levels, and suppressed fibrotic markers (α-SMA, FN1).
- METTL3 mediated the m6A modification of circ_0044226, and its downregulation mitigated ferroptosis, alleviating pulmonary fibrosis in a rat model.
Conclusions:
- The METTL3/circ_0044226 axis plays a significant role in the pathogenesis of pulmonary fibrosis by regulating ferroptosis.
- Targeting the METTL3/circ_0044226 pathway presents a promising therapeutic strategy for mitigating pulmonary fibrosis.
- Inhibition of ferroptosis via this axis offers a novel approach to treating IPF.
