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[摘要] 目的 观察胃癌组织中微小RNA-181a（miR-181a）与其靶基因共济失调-毛细血管扩张突变基因（ATM）的表达与异常情况，初步研究其意义。 方法 收集2009年4月～2011年12月广州市第一人民医院外科手术切除的胃癌组织标本9例，同时选取其癌旁非癌组织标本作为对照，分析胃癌组织中miR-181a与ATM蛋白表达的相关性。提取其蛋白质及总RNA，采用实时荧光定量PCR（qRT-PCR）检测标本的miR-181a，Western blot检测ATM蛋白。比较胃癌组织及癌旁非癌组织中miR-181a、ATM蛋白表达量。 结果 miR-181a在胃癌组织中的表达量为（1.981±1.800），miR-181a在邻近非癌组织中的表达量为（0.394±0.093）；灰度值检测：癌组织ATM蛋白为（0.2539±0.0046）；非癌组织为（0.5525±0.0660），癌及非癌组织中miR-181a、ATM蛋白表达量比较，差异均有高度统计学意义（P < 0.01）；miR-181a与ATM蛋白表达呈负相关（r=-0.539，P < 0.01）。 结论 miR-181a在胃癌组织中表达明显增高，ATM蛋白表达明显下降；究其原因可能是通过基因沉默机制miR-181a降低ATM蛋白表达量，从而在胃癌的发生及发展中起促进作用。

[关键词] 共济失调-毛细血管扩张突变基因；胃癌；微小RNA；miR-181a

[中图分类号] R735.2 [文献标识码] A [文章编号] 1673-7210（2015）05（c）-0024-05

[Abstract] Objective To investigate the expression and significance of microRNA （miRNA）-181a （miR-181a） and its target gene ATM in gastric carcinoma tissues. Methods Tissues of gastric carcinoma and adjacent non-tumorous were collected respectively from 9 patients given surgical operation in Guangzhou First People's Hospital from April 2009 to December 2011. The total RNA and protein were extracted routinely， the miR-181a was detected by Real-time quantitative PCR， ATM protein was detected by Western blot. The expression of miR-181a and ATM protein between gastric carcinoma and adjacent non-tumorous were compared， and the correlation between miR-181a and ATM protein levels in gastric carcinoma was analyzed. Results In gastric carcinoma tissues， the expression of miR-181a and ATM protein were （1.981±1.800）， （0.2539±0.0046） respectively， whereas in the adjacent non-tumorous tissues， the expression of miR-181a and ATM protein were （0.394±0.093）， （0.5525±0.0660） respectively. The differences between the expression of miR-181a and ATM protein in these two tissues were statistically significant （P < 0.01）. There was a negative correlation between miR-181a and ATM protein levels （r=-0.539， P < 0.01）. Conclusion The expression of miR-181a is significantly up-regulated in gastric carcinoma tissues， whereas the ATM protein is markedly decreased. miR-181a may inhibit ATM expression by post-transcriptional gene silencing to restrain gastric carcinoma occurrence and progress.

[Key words] ATM； Gastric cancer， micro-RNA； miR-181a

微小RNA（microRNA）是一类非编码小分子 RNA，存在于真核生物中，长度约为22个核苷酸，有高度的进化保守性，以碱基互补配对原则与靶基因mRNA结合，从而引起靶基因mRNA的降解或抑制靶基因mRNA的翻译，进而在转录后完成对基因表达的调控，在多种肿瘤的发生发展过程中作为一类潜在的癌基因或抑癌基因发挥作用[1-2]。作为miR-181家族新成员，miR-181a是近期才发现的一个micro-RNA，它在胸腺细胞中表达上调，而在人白血病K562细胞及神经胶质瘤中表达下调，在许多疾病中，如慢性淋巴细胞性白血病、非小细胞肺癌和恶性胶质瘤等诸多疾病的研究方面较多且较为深入，但在胃癌研究方面的报道甚少。共济失调-毛细血管扩张症突变基因（Ataxia-telangiectasia mutated gene，ATM）被认为是一种抑癌基因[3-5]，ATM的基因突变增加癌症患者的易感风险，最初的研究在乳腺癌和胃癌[4，6-7]和ATM蛋白能抑制人类乳腺上皮细胞的恶性转化[8]。……