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首页> 外文期刊>The FEBS journal >MicroRNA-182 targets cAMP-responsive element-binding protein 1 and suppresses cell growth in human gastric adenocarcinoma
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MicroRNA-182 targets cAMP-responsive element-binding protein 1 and suppresses cell growth in human gastric adenocarcinoma

机译：MicroRNA-182靶向cAMP反应元件结合蛋白1，并抑制人胃腺癌中的细胞生长

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摘要

MicroRNAs (miRNAs) constitute a class of noncoding RNAs that post-transcriptionally regulate gene expression. Recent evidence indicates that many miRNAs function as oncogenes or tumor suppressors by negatively regulating their target genes. In our previous study, using miRNA microarray analysis, we found that miRNA-182 (miR-182) was significantly downregulated in human gastric adenocarcinoma tissue samples. Here, we confirmed the downregulation of miR-182 in a larger sample of gastric tissue samples. Overexpression of miR-182 suppressed the proliferation and colony formation of gastric cancer cells. An oncogene, encoding cAMP-responsive element binding protein 1 (CREB1), serves as a direct target gene of miR-182. A fluorescent reporter assay confirmed that miR-182 binds specifically to the predicted site of the CREB1 mRNA 3'-UTR. When miR-182 was overexpressed in gastric cancer cell lines, both the mRNA and protein levels of CREB1 were depressed. Furthermore, CREB1 was present at a high level in human gastric adenocarcinoma tissues, and this was inversely correlated with miR-182 expression. Ectopic expression of CREB1 overcame the suppressive phenotypes of gastric cancer cells caused by miR-182. These results indicate that miR-182 targets the CREB1 gene and suppresses gastric adenocarcinoma cell growth, suggesting that miR-182 shows tumor-suppressive activity in human gastric cancer.
机译：MicroRNA（miRNA）构成了一类非转录RNA，可在转录后调节基因表达。最近的证据表明，许多miRNA通过负调控其靶基因而起癌基因或抑癌作用。在我们先前的研究中，使用miRNA芯片分析，我们发现人胃腺癌组织样品中的miRNA-182（miR-182）明显下调。在这里，我们证实了胃组织样品中的较大样品中miR-182的下调。 miR-182的过表达抑制了胃癌细胞的增殖和集落形成。编码cAMP响应元件结合蛋白1（CREB1）的癌基因充当miR-182的直接靶基因。荧光报告基因测定证实，miR-182与CREB1 mRNA 3'-UTR的预测位点特异性结合。当miR-182在胃癌细胞系中过度表达时，CREB1的mRNA和蛋白水平均下降。此外，CREB1在人胃腺癌组织中高水平存在，并且与miR-182表达呈负相关。 CREB1的异位表达克服了miR-182引起的胃癌细胞的抑制表型。这些结果表明，miR-182靶向CREB1基因并抑制胃腺癌细胞生长，表明miR-182在人胃癌中显示出肿瘤抑制活性。

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