MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis.
MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis.
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DOI：
10.1111/cas.12330
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发表时间：
2014-02
期刊：
影响因子：
5.7
通讯作者：
Yasui W
中科院分区：
文献类型：
--
作者：
Sakamoto N;Naito Y;Oue N;Sentani K;Uraoka N;Oo HZ;Yanagihara K;Aoyagi K;Sasaki H;Yasui W
胃癌（GC）是通过基因表达失调和表观遗传异常的积累而发展的，导致肿瘤细胞获得恶性特征。microRNA（miRNAs）在癌症发展中起着关键作用，它们可以作为致癌基因或抑癌基因。为了鉴定与胃癌临床病理特征相关和/或参与肿瘤进展的miRNA，采用miRNA微阵列技术检测了20例胃癌组织和5例相应的非肿瘤性胃粘膜中miRNA的表达。利用寡核苷酸芯片技术对miRNA靶点进行预测。通过定量RT-PCR、Western blotting、报告基因分析和细胞侵袭实验分析候选miRNAs及其靶基因的功能。miRNA表达谱的比较显示，在大多数GC组织中发现了miR-148 a的下调。miR-148 a的下调与晚期临床分期、淋巴结转移和不良临床结局显著相关。自定义寡核苷酸阵列分析显示，MMP 7的表达显着下调miR-148 a过表达的GC细胞; MMP 7被发现是一个直接的和功能性的目标，miR-148 a，参与细胞侵袭。这些结果表明，miR-148 a有助于维持正常胃组织的稳态，并通过调节MMP 7的表达在GC侵袭中起重要作用。
Gastric cancer (GC) develops through deregulation of gene expression and accumulation of epigenetic abnormalities, leading to tumor cell acquisition of malignant features. MicroRNAs (miRNAs) play a critical role in cancer development where they can act as oncogenes or oncosuppressors. To identify miRNAs that are associated with some clinicopathologic features of GC and/or participate in tumor progression, miRNA expression in 20 GC tissues and five corresponding non-neoplastic gastric mucosa was examined by miRNA microarray. Oligonucleotide array analysis was carried out for miRNA target prediction. The functions of candidate miRNAs and their target genes were also analyzed by quantitative RT-PCR, Western blotting, reporter gene assay, and cell invasion assay. Comparison of miRNA expression profiles revealed that downregulation of miR-148a was identified in most of the GC tissues. Downregulation of miR-148a was significantly correlated with an advanced clinical stage, lymph node metastasis, and poor clinical outcome. Custom oligonucleotide array analysis revealed that MMP7 expression was markedly downregulated in miR-148a-overexpressing GC cells; MMP7 was found to be a direct and functional target of miR-148a, participating in cell invasion. These results suggest that miR-148a contributes to the maintenance of homeostasis in normal stomach tissue and plays an important role in GC invasion by regulating MMP7 expression.
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影响因子：
14.9
作者：
Thomson DW;Bracken CP;Goodall GJ
通讯作者：
Goodall GJ
影响因子：
8
作者：
Aprelikova, O.;Palla, J.;Hibler, B.;Yu, X.;Greer, Y. E.;Yi, M.;Stephens, R.;Maxwell, G. L.;Jazaeri, A.;Risinger, J. I.;Rubin, J. S.;Niederhuber, J.
通讯作者：
Niederhuber, J.
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
13.6
作者：
Di Leva G;Croce CM
通讯作者：
Croce CM
影响因子：
6.4
作者：
Fanelli, Marcello Ferretti;Chinen, Ludmilla T. Domingos;Montagnini, Andre Luis
通讯作者：
Montagnini, Andre Luis