Xie Jiaxiang, Zhang Jingqi, Xiong Gan, Ouyang Shengqi, Yun Bokai, Xu Xiuyun, Wang Wenjin, Zhang Ming, Xie Nan, Chen Demeng, Wang Cheng
Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
Oral Dis. 2024 Jul;30(5):3212-3224. doi: 10.1111/odi.14762. Epub 2023 Oct 5.
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.
BRD4属于溴结构域额外末端（BET）蛋白家族，在肿瘤进展中发挥独特作用。然而，BRD4在成釉细胞瘤（AM）中的潜在影响仍 largely未知。在此，我们旨在评估BRD4在AM中的表达及功能作用。
通过免疫组化评估BRD4的表达水平。通过一系列实验评估AM细胞的增殖、迁移、侵袭及致瘤能力。为探究BRD4缺失的AM细胞的分子表达谱，进行了RNA测序（RNA-seq）。对从基因表达综合数据库（GEO）获得的AM表达矩阵进行生物信息学分析。用AM患者来源的类器官评估BET抑制剂（BETi）的治疗效果。
在传统AM、复发性AM和成釉细胞癌中观察到BRD4上调。BRD4缺失抑制了AM的增殖、侵袭、迁移及肿瘤发生。给予BETi可减弱AM的侵袭性及AM患者来源类器官的生长。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其复发。这些发现凸显BRD4作为AM治疗中一个有前景的治疗靶点。
