BRD4属于溴结构域额外末端（BET）蛋白家族，在肿瘤进展中发挥着独特的作用。然而，BRD4 对成釉细胞瘤 (AM) 的潜在影响仍然很大程度上未知。在此，我们的目的是评估 BRD4 在 AM 中的表达和功能作用。通过免疫组织化学评估 BRD4 的表达水平。通过一系列测定评估AM细胞的增殖、迁移、侵袭和致瘤能力。为了探索 BRD4 耗尽的 AM 细胞的分子表达谱，进行了 RNA 测序 (RNA-seq)。对从基因表达综合库 (GEO) 获得的 AM 表达矩阵进行生物信息学分析。使用 AM 患者来源的类器官评估 BET 抑制剂 (BETi) 的治疗效果。在常规 AM、复发性 AM 和成釉细胞癌中观察到 BRD4 上调。 BRD4 的缺失抑制了 AM 的增殖、侵袭、迁移和肿瘤发生。 BETi 的施用减弱了 AM 的侵袭性和 AM 患者来源的类器官的生长。生物信息学分析表明，BRD4可能通过调节Wnt通路和干性相关通路促进AM进展。BRD4通过调节Wnt通路和干性相关通路增加成釉细胞瘤的侵袭性并促进成釉细胞瘤的复发。这些发现凸显了 BRD4 作为 AM 管理中一个有前途的治疗靶点。© 2023 Wiley periodicals LLC。

BRD4, belonging to the bromodomain extra-terminal (BET) protein family, plays a unique role in tumor progression. However, the potential impact of BRD4 in ameloblastoma (AM) remains largely unknown. Herein, we aimed to assess the expression and functional role of BRD4 in AM.The expression level of BRD4 was assessed by immunohistochemistry. The proliferation, migration, invasion, and tumorigenic abilities of AM cells were assessed by a series of assays. To explore the molecular expression profile of BRD4-depleted AM cells, RNA sequencing (RNA-seq) was performed. Bioinformatic analysis was performed on AM expression matrices obtained from the Gene Expression Omnibus (GEO). The therapeutic efficacy of BET-inhibitors (BETi) was assessed with AM patient-derived organoids.Upregulation of BRD4 was observed in conventional AMs, recurrent AMs, and ameloblastic carcinomas. Depletion of BRD4 inhibited proliferation, invasion, migration, and tumorigenesis in AM. Administration of BETi attenuated the aggressiveness of AM and the growth of AM patient-derived organoids. Bioinformatic analysis indicated that BRD4 may promote AM progression by regulating the Wnt pathway and stemness-associated pathways.BRD4 increases the aggressiveness and promotes the recurrence of ameloblastoma by regulating the Wnt pathway and stemness-associated pathways. These findings highlight BRD4 as a promising therapeutic target in AM management.© 2023 Wiley Periodicals LLC.