microRNA-24靶向RegⅣ抑制胃癌细胞生长与转移  

microRNA-24 inhibits growth and metastasis of gastric cancer cell by targeting Reg Ⅳ

作　　者：段衍涛[1] 刘兵[1] 俞焙秦[1] 李建芳[1] 燕敏[1] 于颖彦[1] 刘炳亚[1] 朱正纲[1] 项明[1] 杨秋蒙[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院外科上海消化外科研究所上海市胃肿瘤重点实验室,上海200025

出　　处：《外科理论与实践》2013年第1期25-30,共6页Journal of Surgery Concepts & Practice

基　　金：国家自然科学基金(81172324);教育部博士点基金(博导类)(20110073110071);国家支撑计划(2011BA203191);上海市教委重点(12ZZ102;12ZZ105);上海市科委基础重点(10jc1411100)

摘　　要：目的:探讨microRNA-24(miR-24)在胃癌中的作用及其作用靶基因。方法 :采用qRT-PCR的方法检测miR-24在9株胃癌细胞和永生化胃黏膜上皮细胞GES-1中的表达,同时检测63例病人的胃癌组织及相应的癌旁正常组织中miR-24的表达,分析miR-24与胃癌临床病理特征之间的关系。应用miR-24模拟体转染胃癌细胞株,使其过表达miR-24,细胞增殖试验(CCK-8法)、流式细胞技术(Annexin-Ⅴ/PI标记)、Transwell试验检测上调胃癌细胞株miR-24表达后细胞增殖、凋亡、迁移和周期的变化;并用ELISA技术和双荧光素酶基因报告载体检测miR-24是否调控RegⅣ的表达。结果:54.0%(34/63)胃癌病人的miR-24在肿瘤组织中表达,与相应的癌旁正常组织相比下降,且miR-24在肿瘤组织中的表达与胃癌的组织分化程度相关(r=0.292,P=0.021),与其他的临床病例特征如年龄、性别、浸润深度、淋巴结转移和TNM分期没有相关性。miR-24抑制胃癌细胞的生长与转移,且促进胃癌细胞的凋亡。miR-24可降低RegⅣ的蛋白表达水平。结论:miR-24抑制胃癌的发生、发展,miR-24可能通过调控RegⅣ的表达来发挥其生物学效应。RegⅣ与miR-24均在胃癌的发生、发展中发挥了重要作用。Objective To investigate the role of miR-24 in gastric cancer development and its targeting genes. Methods The expression of miR-24 were determined in 9 gastric cancer cell lines, immortalized gastric mucous epithelial cell GES-1 and in tumor tissues and its matched adjacent non-tumor tissues from 63 patients with gastric cancer by qRT- PCR. The relationship was analyzed between the expression of miR-24 and the clinicopathological parameters of gastric cancer. The influence on the proliferation, apoptosis, migration and cell cycle in gastric cancer cell of miR-24 overexpression was investigated and evaluated by CCK-8 kit, Annexin-V ＋PI or Transwell test. ELISA and luciferase reporter assay were performed to evaluate the regulation of RegiV expression by miR-24. Results In 54.0%（34/63） cases of gastric cancer, miR-24 expression was down-regulated in tumor tissues compared to its matched adjacent non-tumor tissues. The expression of miR-24 was associated with tissue differentiation（r=0.292, P=0.021）. There was no relationship between the miR-24 expression and other elinicopathological features such as age, gender, infiltration depth, lymph node metastasis or TNM stage, miR-24 inhibited proliferation and migration of gastric cancer cells, but promote apoptosis, miR- 24 inhibited the protein level of ReglV. Conclusions miR-24 inhibits the pathogenesis and development of gastric cancer. miR-24 may exert its biological effects through regulation on ReglV expression. Both ReglV and miR-24 play important roles in the Dathozenesis and development of gastric cancer.

关 键 词：胃癌 ReglV microRNA-24 生长 转移 

分 类 号：R735.2[医药卫生—肿瘤]