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Archive > Volume 33 Issue 6 > 2026,33(6):619-629. DOI:10.3872/j.issn.1007-385X.2026.06.004 Prev Next
Basic Research
BRD1 promotes non-small cell lung cancer cell proliferation and migration by regulating the ITGA2-AKT axis
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Abstract:
[Abstract] Objective: To investigate the role of bromodomain-containing protein 1 (BRD1) in the progression of non-small cell lung cancer (NSCLC) and its underlying mechanism through regulation of the PI3K/AKT signaling pathway. Methods: The predictive value of BRD1 as an immunotherapeutic biomarker was assessed using the TIMER 3.0 database. Human NSCLC cell lines A549 and NCI-H1299 stably overexpressing BRD1 or the N-terminal truncated mutant BRD1- ΔN were established using a lentiviral system. CCK-8, colony formation, wound healing, and Transwell assays were used to assess the effects of BRD1/BRD1-ΔN overexpression on cell proliferation and migration. Flow cytometry and Western blotting were used to detect cell apoptosis and the expression of apoptosis- related proteins. RNA-seq was employed to screen the signaling pathways affected by BRD1/BRD1- ΔN overexpression. Western blotting and in vitro kinase assays were used to detect the activation of AKT signaling pathways by overexpressing BRD1/BRD1-ΔN. To determine whether BRD1/BRD1-ΔN promotes cell proliferation and migration in an AKT-dependent manner, the AKT inhibitor · · 619 [[PAGE_INDEX=2 FILE=08b612ef-59ff-47e1-960e-f599d97bfff7.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) LY294002 was applied to NCI-H1299 cells overexpressing BRD1/BRD1- ΔN, followed by functional assays (CCK-8 and wound healing). RNA-seq combined with KEGG/GSEA analysis, co-immunoprecipitation (Co-IP), and RT-qPCR were performed to identify and validate integrin alpha-2 (ITGA2) as a key mediator that facilitates AKT activation. Co-IP, lentivirus-mediated ITGA2 knockdown, Western blotting, and functional experiments were then used to clarify the specific role of ITGA2 in BRD1-mediated AKT activation. Results: Database analysis showed that BRD1 could serve as a moderate predictive biomarker for immunotherapy in NSCLC (AUC = 0.625). Overexpression of BRD1/BRD1- ΔN significantly enhanced the proliferation and migration of NSCLC cells (all P < 0.01) without affecting apoptosis or the expression of apoptosis-related proteins (all P > 0.05). RNA-seq analysis indicated that BRD1/BRD1- ΔN overexpression primarily resulted in enrichment of the PI3K/AKT signaling pathway. Western blotting and in vitro kinase assays demonstrated that BRD1/BRD1-ΔN overexpression did not affect the phosphorylation of PDK1, an upstream kinase of AKT, nor alter the acetylation level of AKT (all P > 0.05). Treatment with the AKT inhibitor LY294002 revealed that BRD1/BRD1-ΔN promoted cell proliferation and migration partially through AKT activation. RT-qPCR and Western blotting confirmed that BRD1 overexpression upregulated ITGA2 at both mRNA and protein levels. Silencing ITGA2 reversed BRD1-induced AKT activation and the enhanced cell proliferation and migration. Conclusion: BRD1 is a novel oncogenic driver in NSCLC. It activates the AKT signaling pathway by upregulating ITGA2, thereby promoting the proliferation and migration of lung cancer cells.
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