Decreased Expression of MicroRNA-143 and -145 in Human Gastric Cancers

Decreased Expression of MicroRNA-143 and -145 in Human Gastric Cancers
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DOI:
10.1159/000218166
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发表时间:
2009-01-01
期刊:
影响因子:
3.5
通讯作者:
Akao, Yukihiro
Akao, Yukihiro
中科院分区:
医学3区
文献类型:
--
作者:
Takagi, Takeshi;Iio, Akio;Akao, Yukihiro

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目的:在人类肿瘤中存在特异性microRNAs(miRNAs)的下调,提示miRNAs在肿瘤抑制中的作用。我们研究了miRNAs miR-143和miR-145在胃癌中的作用。研究方法:采用TaqMan荧光定量PCR方法检测43例胃癌患者组织中miR-143和miR-145的表达水平。通过用miRNA转染人胃癌细胞来评估生长抑制作用。结果如下:miR-143和-145的表达水平在大多数人胃癌中降低,如先前报道的在结肠肿瘤中发生的那样。用miR-145转染人胃MKN-1细胞比用miR-143转染人胃MKN-1细胞产生更大的生长抑制作用,结果与结肠癌相反。在MKN-1细胞中,通过联合转染miR-143和miR-145显示了对生长抑制的累加效应;此外,在转染miR-143或miR-145后还观察到对5-氟尿嘧啶的更高敏感性。miR-145可能的候选靶信使RNA被鉴定为胰岛素受体底物-1和beta-actin。结论:miR-143和miR-145在胃肠道肿瘤中起抗肿瘤作用。版权所有(C)2009 S. Karger AG,巴塞尔
Objective: Downregulation of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. We investigated the role of the miRNAs miR-143 and miR-145 in gastric cancers. Methods: The expression levels of miR-143 and miR-145 in the samples from 43 patients with gastric cancer were determined by real-time PCR using TaqMan assay. The growth inhibitory effect was estimated by the transfection of human gastric cancer cells with the miRNA. Results: The expression levels of miR-143 and -145 were decreased in most human gastric cancers examined, as previously reported to occur in colon tumors. The transfection of human gastric MKN-1 cells with miR-145 resulted in a greater growth inhibitory effect than that with miR-143, results which were contrary to those in colon cancers. In MKN-1 cells, an additive effect on growth inhibition was shown by the combined transfection with miR-143 and miR-145; further, higher sensitivity to 5-fluorouracil was also observed following the transfection with miR-143 or miR-145. The possible candidate target messenger RNAs of miR-145 were identified to be insulin receptor substrate-1 and beta-actin. Conclusion: Taken together, these findings suggest that miR-143 and miR-145 act as anti-on-comirs common to gastrointestinal tumors. Copyright (C) 2009 S. Karger AG, Basel