Steroid receptor coactivator-1 facilitates METTL3-mediated m6A modification by coactivating NF-κB and promotes the malignant progression of glioblastoma
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View abstract on PubMed
Summary
This summary is machine-generated.Steroid receptor coactivator-1 (SRC-1) promotes glioblastoma (GBM) progression by regulating N6-methyladenosine (m6A) RNA modification of c-Myc. Targeting SRC-1 or its pathway offers potential new glioblastoma therapies.
Area Of Science
- Oncology
- Molecular Biology
- Epigenetics
Background
- Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options.
- The role of steroid receptor coactivator-1 (SRC-1) in GBM pathogenesis and its connection to RNA modifications like N6-methyladenosine (m6A) are not well understood.
Purpose Of The Study
- To investigate the impact of SRC-1 on m6A RNA modification and its contribution to GBM progression.
- To elucidate the molecular mechanisms by which SRC-1 influences GBM malignancy.
Main Methods
- Analysis of CGGA database for SRC-1 and METTL3 correlation.
- In vitro assays (dot blot, MeRIP-qPCR, proliferation, migration, cell cycle, apoptosis assays) to assess SRC-1 function.
- In vivo xenograft mouse models to evaluate tumor growth.
- Molecular assays including Co-IP, immunofluorescence, dual-luciferase, and ChIP-qPCR.
Main Results
- SRC-1 positively correlates with METTL3 expression in GBM and enhances global m6A RNA modification.
- SRC-1 knockdown inhibits GBM cell proliferation, migration, and survival by suppressing METTL3-mediated c-Myc m6A methylation and stability.
- SRC-1 interacts with NF-κB, which activates METTL3 promoter activity, leading to increased c-Myc m6A modification and GBM progression.
- Inhibition of SRC-1 or its pathway (e.g., with bufalin) reduces GBM progression.
Conclusions
- SRC-1 promotes GBM progression through a mechanism involving NF-κB-mediated activation of METTL3, leading to aberrant m6A modification of c-Myc.
- This study identifies SRC-1 as a key regulator in GBM and suggests targeting the SRC-1/NF-κB/METTL3/c-Myc axis as a potential therapeutic strategy for GBM.
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