胆囊癌（GBC）是一种高度恶性的消化道肿瘤，目前缺乏有效的治疗方法。Foxhead box A2（FOXA2）是一种在多种人类恶性肿瘤中表达较低的抑癌基因。本研究旨在确定FOXA2在GBC中的表达情况及其与肿瘤转移的相关性，并通过上皮-间质转化（EMT）作为切入点来阐明其调控机制，以寻找潜在的GBC治疗靶点。首先，使用免疫组化（IHC）检测GBC组织中的FOXA2表达，并将其与临床病理特征和生存预后进行相关性分析。随后，利用划痕、Transwell、RT-PCR和Western blot等实验方法结合动物实验评估FOXA2对GBC细胞迁移和侵袭以及EMT的影响。最后，进行mRNA测序以识别FOXA2在控制GBC细胞EMT过程中的关键下游靶基因，并利用双荧光素酶报告基因和染色质免疫沉淀等实验方法确定其调控机制。实验结果显示，GBC组织中FOXA2表达下调，与肿瘤分期、淋巴结转移和患者预后呈负相关。FOXA2在体内和体外对GBC的EMT和转移具有抑制作用。FOXA2可以通过正向调控丝氨酸蛋白激酶抑制物B5（SERPINB5）的表达来阻碍GBC细胞的迁移和侵袭功能以及EMT过程。FOXA2直接结合到SERPINB5启动子区域以刺激其转录，从而调控GBC细胞的迁移、侵袭行为和EMT过程，可能是一种有效的GBC治疗靶点。©2023 Wiley Periodicals LLC.

Gallbladder cancer (GBC), a highly malignant gastrointestinal tumor, lacks effective therapies. Foxhead box A2 (FOXA2) is a tumor suppressor that is poorly expressed in various human malignancies. This study aimed to ascertain FOXA2 expression in GBC and its relevance to tumor metastasis, and to elucidate its regulatory mechanism with epithelial-mesenchymal transition (EMT) as an entry point, in the hope of providing a potential therapeutic target for GBC.FOXA2 expression in GBC tissues was first detected using immunohistochemistry (IHC), followed by correlation analysis with clinicopathological characteristics and survival prognosis. Subsequently, the effects of FOXA2 on GBC cell migration and invasion, as well as EMT induction, were evaluated by scratch, Transwell, RT-PCR, and Western blot assays, together with animal experimentation. Ultimately, mRNA sequencing was carried out to identify the key downstream target genes of FOXA2 in controlling the EMT process in GBC cells, and dual-luciferase reporter and chromatin immunoprecipitation assays were used to determine its regulatory mechanism.FOXA2 was underexpressed in GBC tissues and inversely correlated with tumor node metastasis stage, lymph node metastasis, and poor patient prognosis. FOXA2 exerts suppressive effects on EMT and metastasis of GBC in vivo and in vitro. FOXA2 can impede GBC cell migratory and invasive functions and EMT by positively mediating serine protein kinase inhibitor B5 (SERPINB5) expression.FOXA2 directly binds to the SERPINB5 promoter region to stimulate its transcription, thereby modulating the migration and invasion behaviors of GBC cells as well as the EMT process, which might be an effective therapeutic target against GBC.© 2023 Wiley Periodicals LLC.