核内不均一性核糖核蛋白A2/B1在胰腺癌中的表达及其对B细胞淋巴瘤/白血病-X选择性剪切的调控机制  

The expression of heterogeneous nuclear ribonucleoprotein A2/B1 in pancreatic cancer and its roles in B cell lymphoma/leukemia-X alternative splicing

作　　者：江艳[1] 刘炜[1] 陈志宇[1] 

机构地区：[1]第三军医大学西南医院全军肝胆外科研究所,重庆400038

出　　处：《中华实验外科杂志》2015年第1期12-14,F0003,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金面上项目（81472775）

摘　　要：目的 探讨核内不均一性核糖核蛋白（hnRNP） A2/B1作为下游靶蛋白参与Fyn诱导的胰腺癌细胞B细胞淋巴瘤/白血病-X（bcl-X）选择性剪切调控的作用及其机制.方法 通过免疫组织化学方法观察28例胰腺癌标本hnRNP A2/B1的表达,并探讨其与胰腺癌临床病理参数之间的关系.通过RNA-免疫共沉淀技术,探讨受Fyn活性调控的hnRNP A2/B1的下游靶基因.通过改变hnRNP A2/B1的表达,观察对bcl-X选择性剪切的影响.结果 28例胰腺癌组织标本中有23例出现hnRNP A2/B1的表达,表达水平与胰腺癌TNM分期（R =0.854,P＜0.05）、是否发生远处转移（R =0.698,P＜0.05）相关等因素有关.RNA-免疫共沉淀证实,hnRNP A2/B1能够与BxPC3细胞中bcl-X基因的Pre-mRNA结合.hnRNP A2/B1表达水平的改变参与BxPC3胰腺癌细胞中bcl-X两种剪切体比例的调控.结论 hnRNP A2/B1的表达水平与胰腺癌组织侵袭转移能力密切相关;hnRNPA2/B1可以与胰腺癌细胞中bcl-X基因结合,从而影响bcl-X选择性剪切.Objective To explore the expression of heterogeneous nuclear ribonucleoprotein （hnRNP） A2/B1 and its roles of in B cell lymphoma/leukemia-X （bcl-X）.alternative splicing in pancreatic cancer cells.Methods immunohistochemistry was performed to explore hnRNP A2/B1 expression and its relationship with pathology parameters in 26 pancreatic cancer tissue samples.RNA immunoprecipitation was performed to search the downstream target genes of hnRNP A2/B1.Roles of hnRNP A2/B1 in bcl-X alternative splicing was assessed by hnRNP A2/B1 overexpression or knockdown.Results 23 pancreatic cancer tissues showed hnRNP A2/B1 expression,which is correlated with tumor TNM staging and metastasis.RNA immunoprecipitation proved that hnRNP A2/B1 binds to bcl-X pre-mRNA.The change of hnRNP A2/B1 expression modulates bcl-X alternative splicing in pancreatic cancer cells.Conclusion The expression of hnRNP A2/B1 is correlated with pancreatic cancer invasion and metastasis.HnRNP A2/B1 bind to bcl-X pre-mRNA and modulates its alternative splicing.

关 键 词：核内不均一性核糖核蛋白A2/B1 B细胞淋巴瘤/白血病-X 选择性剪切 胰 腺癌 

分 类 号：R735.9[医药卫生—肿瘤] R733[医药卫生—临床医学]