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miR-125b靶向MCL1抑制胃癌 MGC-803细胞增殖
MiR-125b Targeting MCL1 Inhibits Proliferation of Gastric Cancer Cell Line MGC-803
投稿时间:2017-04-13  修订日期:2018-01-18
中文关键词:  胃癌,miR-125b,MCL1基因,细胞增殖
英文关键词:gastric cancer, miR-125b, MCL1 gene, cell proliferation
基金项目:湖南省高校创新平台基金(12K094, 13K083),湖南省科技厅项目(2015SK20203),湖南省教育厅课题(11C1112),湖南省研究生科研创新项目(CX2016B478)和南华大学博士科研启动基金(2016XQD21)和南华大学基础医学湖南省重点学科基金资助项目
作者单位E-mail
胡泽刚 南华大学医学院肿瘤研究所肿瘤细胞与分子病理学湖南省重点实验室 肿瘤细胞与分子病理学湖南省高校重点实验室衡阳 421001 bl8281075@qq.com 
伍石华 邵阳学院附属医院病理科邵阳 422000  
刘重元 南华大学医学院肿瘤研究所肿瘤细胞与分子病理学湖南省重点实验室 肿瘤细胞与分子病理学湖南省高校重点实验室衡阳 421001  
谢黎明 南华大学附属第一医院衡阳 421001  
张和良 南华大学医学院肿瘤研究所肿瘤细胞与分子病理学湖南省重点实验室 肿瘤细胞与分子病理学湖南省高校重点实验室衡阳 421001  
肖玄 南华大学医学院临床医学卓越医师班本科生衡阳 421001  
张志伟 南华大学医学院肿瘤研究所肿瘤细胞与分子病理学湖南省重点实验室 肿瘤细胞与分子病理学湖南省高校重点实验室衡阳 421001 nhdxzzw@qq.com 
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中文摘要:
      探讨miR-125b对胃癌MGC-803细胞增殖的影响及机制,为阐明胃癌发病的分子机制提供实验依据.采用qRT-PCR和原位杂交,检测miR-125b在正常胃黏膜(NGM)和胃癌(GAC)组织中的表达.将miR-125b导入胃癌MGC-803细胞,观察miR-125b高表达对MGC-803细胞增殖的影响.利用Targetscan 6.2软件及荧光素酶报告基因检测,分析miR-125b对MCL1基因的靶向性作用.构建MCL1干扰载体,观察干扰MCL1基因表达对MGC-803细胞增殖的影响.结果发现,miR-125b在胃癌组织中低表达,其表达与胃癌的分化程度及患者预后呈正相关,与TNM分期、淋巴结转移呈负相关(P < 0.01).miR-125b高表达后MGC-803细胞的增殖降低、凋亡率增加、裂解caspase-3与裂解PARP表达增加(P < 0.01);miR-125b与MCL1基因的3′UTR (2 613~2 620)结合,抑制MCL1的mRNA及蛋白质表达(P < 0.01);沉默MCL1基因表达后MGC-803细胞的增殖降低、凋亡率增加、裂解caspase-3与裂解PARP表达增加(P < 0.01).从而得出结论,miR-125b在胃癌组织中低表达,其表达与胃癌组织分化程度、TNM分期、淋巴结转移及患者预后密切相关;miR-125b靶向抑制MCL1基因表达,活化caspase-3信号通路,抑制MGC-803细胞增殖.
英文摘要:
      This research aimed to investigate the effects and mechanism of miR-125b on the proliferation of gastric cancer cell line MGC-803, and to provide the experimental basis for elucidating the molecular mechanism of gastric cancer. The expression of miR-125b was detected by qRT-PCR and in situ hybridization in NGM and GAC tissues. The miR-125b was transfected in gastric cancer MGC-803 cells. The effects of over-expression of miR-125b to the proliferation of gastric cancer MGC-803 cells were observed. The targeting effect of miR-125b on MCL1 gene was analyzed by Targetscan 6.2 software and luciferase reporter gene assay. The interference vector of MCL1 was constructed. The effects of interference expression of MCL1 to the proliferation of gastric cancer MGC-803 cells were observed. We found the expression of miR-125b was low in gastric cancer tissues. The low-expression of miR-125b was positively correlated with the degree of differentiation and prognosis of patients, and negative correlation with TNM staging and lymph node metastasis of gastric cancer (P < 0.01). The proliferation of MGC-803 cells decreased, and the cell apoptosis rate, cleaved caspase-3 and cleaved PARP cells increased when the miR-125b was over-expression (P < 0.01). MiR-125b binded MCL1-3' UTR (2 613-2 620 nucleotide) and inhibited the expression of MCL1 mRNA and protein in MGC-803 cells after its over-expression (P < 0.01). The proliferation of MGC-803 cells decreased, and the cell apoptosis rate, cleaved caspase-3 and cleaved PARP cells increased when the expression of MCL1 was silenced (P < 0.01). In conclusion, the expression of miR-125b was low, and closely related with the differentiation degree of gastric carcinoma, TNM staging, lymph node metastasis and prognosis of patients in gastric cancer tissues. MiR-125b activated caspase-3 signaling pathway to inhibit the proliferation of MGC-803 cells through targeting the expression of MCL1 gene.
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