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BRD8 promotes non-small cell lung cancer progression by stabilizing MBD2 and activating the MAPK pathway
Li Dong1, Yuchen Zhou2, Qingwei Cui1
1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Cellular Signalling
|July 4, 2026
Summary
Bromodomain-containing protein 8 (BRD8) promotes non-small cell lung cancer (NSCLC) progression by stabilizing methyl-CpG-binding domain protein 2 (MBD2), activating the MAPK pathway. Targeting BRD8 or MBD2 may offer new therapeutic strategies for NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality with limited treatment options.
- Bromodomain-containing protein 8 (BRD8) is an epigenetic regulator implicated in various cancers, but its role in NSCLC is unclear.
- The mitogen-activated protein kinase (MAPK) pathway is crucial in driving NSCLC malignancy.
Purpose of the Study:
- To investigate the biological functions and molecular mechanisms of BRD8 in NSCLC progression.
- To explore the interaction between BRD8 and its downstream effectors.
- To elucidate the role of the BRD8/MBD2 axis in activating the MAPK pathway in NSCLC.
Main Methods:
- Analysis of BRD8 expression in clinical NSCLC tissues and cell lines.
- In vitro functional assays (proliferation, migration, invasion).
- Co-immunoprecipitation, mass spectrometry, ubiquitination assays, and cycloheximide chase assays to study BRD8-MBD2 interaction and MBD2 stability.
- In vivo nude mouse xenograft experiments.
Main Results:
- BRD8 is overexpressed in NSCLC and promotes tumor cell proliferation, migration, and invasion.
- BRD8 directly interacts with MBD2 and enhances its K63-linked ubiquitination and protein stability.
- BRD8-induced MBD2 stabilization activates the MAPK signaling pathway.
- Knockdown of BRD8 or MBD2 suppresses tumor growth and MAPK pathway activity in vivo.
Conclusions:
- BRD8 facilitates NSCLC progression by stabilizing MBD2 via K63-linked ubiquitination, leading to MAPK pathway activation.
- The BRD8/MBD2/MAPK axis represents a novel oncogenic mechanism in NSCLC.
- Targeting BRD8 or MBD2 may provide potential therapeutic strategies for NSCLC.
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