MicroRNA-18a modulates STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis.
MicroRNA-18a modulates STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis.
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DOI：
10.1038/bjc.2012.587
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发表时间：
2013-02-19
影响因子：
8.8
通讯作者：
Kurode, M.
中科院分区：
文献类型：
--
作者：
Wu, W.;Takanashi, M.;Bodigin, N.;Ohno, S-i;Fujita, K.;Hoshino, S.;Osaka, Y.;Tsuchida, A.;Kurode, M.
microRNA（miRNA，miR）-18 a是miR-17-92簇的成员，是一个重要的基因座，在几种癌症中显著过表达，与癌症的发生和进展相关。然而，miR-17-92簇及其单个miRNA的作用机制在很大程度上是未知的。在这项研究中，我们研究了表达的miR-17-92簇的原位杂交（ISH）分析和拷贝数分析在胃组织芯片（TMA）标本。我们确定miR-18 a的水平高于簇中的其他五种miRNA。此外，我们确定了活化信号转导蛋白抑制剂和转录激活因子3（PIAS 3）作为胃癌中miR-18 a的直接靶点。miR-18 a水平与信号转导和转录激活因子3（STAT 3）下游转录靶点Survivin、Bcl-xL和c-Myc水平正相关。STAT 3诱导的转录可由PIAS 3负调控;与此一致，PIAS 3水平与Survivin、Bcl-xL和c-Myc水平呈负相关。我们的研究结果表明，miR-18 a作为一种癌基因，在胃腺癌发生中发挥作用，至少部分通过负调控PIAS 3，从而调节STAT 3靶基因的表达。
MicroRNA (miRNA, miR)-18a is a member of the miR-17–92 cluster, an important locus that is markedly overexpressed in several cancers and associated with cancer development and progression. However, the mechanism of action of the miR-17–92 cluster and its individual miRNAs are largely unknown. In this study, we investigated the expression of the miR-17–92 cluster by in situ hybridisation (ISH) assay and copy-number analysis in gastric tissue microarray (TMA) specimens. We determined that miR-18a was present at higher levels than the other five miRNAs in the cluster. In addition, we identified Protein Inhibitor of Activated Signal Transducer and Activator of Transcription 3 (PIAS3) as a direct target of miR-18a in gastric cancer. miR-18a level was positively correlated with levels of Survivin, Bcl-xL, and c-Myc, which are downstream transcriptional targets of Signal Transducer and Activator of Transcription 3 (STAT3). STAT3-induced transcription can be negatively regulated by PIAS3; consistent with this, PIAS3 level was negatively correlated with levels of Survivin, Bcl-xL, and c-Myc. Our findings indicate that miR-18a acts as an oncogene and plays a role in gastric adenocarcinogenesis, at least in part by negatively regulating PIAS3 and thereby modulating expression of STAT3 target genes.
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影响因子：
15.9
作者：
Epling-Burnette, PK;Liu, JH;Loughran, TP
通讯作者：
Loughran, TP
DOI：
10.1111/j.1440-1746.2008.05666.x
发表时间：
2009-04-01
影响因子：
4.1
作者：
Guo, Junming;Miao, Ying;Wang, Yanjun
通讯作者：
Wang, Yanjun
DOI：
10.1073/pnas.0806202105
发表时间：
2008-09-02
影响因子：
11.1
作者：
Pichiorri, Flavia;Suh, Sung-Suk;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
影响因子：
15.9
作者：
Bromberg, J
通讯作者：
Bromberg, J
DOI：
10.1046/j.1440-1746.2001.02361.x
发表时间：
2001-01-01
影响因子：
4.1
作者：
Chen, JP;Lin, C;Wu, M
通讯作者：
Wu, M