BRD4在胰腺癌发生和发展中的作用  

Role of BRD4 in the occurrence and progression of pancreatic cancer

作　　者：张圆 谢丽 李珏笛 罗雯 刘正华 ZHANG Yuan;XIE Li;LI Juedi;LUO Wen;LIU Zhenghua(Department of Basic Medicine,Changsha Health Vocational College,Changsha 410078,China)

机构地区：[1]长沙卫生职业学院基础医学部,长沙410078

出　　处：《临床与病理杂志》2024年第7期1010-1017,共8页Journal of Clinical and Pathological Research

摘　　要：胰腺癌是一种高侵袭性消化系统恶性肿瘤,严重威胁人类健康。含溴结构域的蛋白质4(bromodomaincontaining protein 4,BRD4)是溴域和外域(bromodomain and extraterminal domain,BET)蛋白家族的成员之一,胰腺癌细胞中过表达的BRD4可诱导核受体亚家族5中的A组成员2(nuclear receptor subfamily 5 group A member 2,NR5A2)表达上调,并进一步增强生长分化因子15(growth differentiation factor 15,GDF15)在胰腺癌中的转录水平,促进胰腺癌细胞增殖、转移和侵袭。微RNA(miRNA)-608可以通过结合BRD4 mRNA的3'-非翻译区直接抑制BRD4的表达,从而显著增加胰腺癌的细胞凋亡;使用吉西他滨和BRD4沉默处理胰腺癌细胞时,能减少吉西他滨的耐药性,显著促进胰腺导管腺癌细胞凋亡。了解BRD4的结构构成,探究BRD4在胰腺癌细胞增殖、侵袭、转移以及癌细胞凋亡和癌细胞耐药等过程中的作用通路及临床应用,可为防治胰腺癌的发生、发展提供新思路。Pancreatic cancer is a highly aggressive malignancy of the digestive system,posing a significant threat to human health.Bromodomain-containing protein 4(BRD4),a member of the bromodomain and extraterminal domain(BET)protein family,is overexpressed in pancreatic cancer cells and induces upregulation of nuclear receptor subfamily 5 group A member 2(NR5A2),which in turn enhances the transcription of growth differentiation factor 15(GDF15),promoting pancreatic cancer cell proliferation,metastasis,and invasion.MicroRNA-608 can directly inhibit BRD4 expression by binding to the 3'-untranslated region(3'-UTR)of BRD4 mRNA,thereby significantly increasing apoptosis in pancreatic cancer cells.When pancreatic ductal adenocarcinoma cells are treated with a combination of gemcitabine and BRD4 silencing,gemcitabine resistance is reduced,and apoptosis is significantly promoted.Understanding BRD4’s structural composition and its role in pancreatic cancer cell proliferation,invasion,metastasis,apoptosis,and drug resistance may provide new insights into preventing and treating pancreatic cancer.

关 键 词：含溴结构域的蛋白质4 胰腺癌 增殖 侵袭转移 凋亡 耐药性 

分 类 号：R735.9[医药卫生—肿瘤]