AUTHOR=Meng Minglu , Ma Yingjiao , Xu Jianguo , Chen Gao , Mahato Roshan Kumar 

TITLE=DNA methylation-mediated FGFR1 silencing enhances NF-κB signaling: implications for asthma pathogenesis

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1433557

DOI=10.3389/fmolb.2024.1433557

ISSN=2296-889X

ABSTRACT=<sec><title>Background</title><p>Fibroblast growth factor receptor 1 (<italic>FGFR1</italic>) is known to play a crucial role in the pathogenesis of asthma, although the precise mechanism remains unclear. This study aims to investigate how DNA methylation-mediated silencing of <italic>FGFR1</italic> contributes to the enhancement of NF-κB signaling, thereby influencing the progression of asthma.</p></sec><sec><title>Methods</title><p>RT-qPCR was utilized to assess <italic>FGFR1</italic> mRNA levels in the serum of asthma patients and BEAS-2B, HBEpiC, and PCS-301-011 cells. CCK8 assays were conducted to evaluate the impact of <italic>FGFR1</italic> overexpression on the proliferation of BEAS-2B, PCS-301-011, and HBEpiC cells. Dual-luciferase and DNA methylation inhibition assays were performed to elucidate the underlying mechanism of <italic>FGFR1</italic> gene in asthma. The MassARRAY technique was employed to measure the methylation levels of the <italic>FGFR1</italic> DNA.</p></sec><sec><title>Results</title><p>Elevated <italic>FGFR1</italic> mRNA levels were observed in the serum of asthma patients compared to healthy controls. Overexpression of <italic>FGFR1</italic> in BEAS-2B cells significantly enhanced cell proliferation and stimulated NF-ĸB transcriptional activity in HERK-293T cells. Furthermore, treatment with 5-Aza-CdR, a DNA demethylating agent, markedly increased the expression of <italic>FGFR1</italic> mRNA in BEAS-2B, PCS-301-011, and HBEpiC cells. Luciferase activity analysis confirmed heightened NF-ĸB transcriptional activity in <italic>FGFR1</italic>-overexpressing BEAS-2B cells and BEAS-2B cells treated with 5-Aza-CdR. Additionally, a decrease in methylation levels in the <italic>FGFR1</italic> DNA promoter was detected in the serum of asthma patients using the MassARRAY technique.</p></sec><sec><title>Conclusion</title><p>Our findings reveal a potential mechanism involving <italic>FGFR1</italic> in the progression of asthma. DNA methylation of <italic>FGFR1</italic> inactivates the NF-ĸB signaling pathway, suggesting a promising avenue for developing effective therapeutic strategies for asthma.</p></sec>