MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression.
MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression.
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DOI：
10.1038/sj.bjc.6605037
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发表时间：
2009-08-18
影响因子：
8.8
通讯作者：
Meijer GA
中科院分区：
文献类型：
--
作者：
Diosdado B;van de Wiel MA;Terhaar Sive Droste JS;Mongera S;Postma C;Meijerink WJ;Carvalho B;Meijer GA
MicroRNA 是小的非编码 RNA 分子，调节肿瘤发生的核心机制。在结直肠肿瘤中，8q和13q增益的组合是与结直肠腺瘤向腺癌进展相关的主要因素之一。对位于 13q31 上的 miR-17-92 簇的功能研究表明，其转录由位于 8q 上的 c-myc 激活，并且具有致癌活性。我们研究了结直肠腺瘤期间 miR-17-92 簇对腺癌进展的贡献。通过实时 RT-PCR 测定了 55 个结直肠肿瘤和 10 个对照中 miR-17-92 簇的表达水平。还通过实时 RT-PCR 测定了 48 个肿瘤中的信使 RNA c-myc 表达，并提供了阵列比较基因组杂交 (aCGH) 数据。与未获得 miR-17-92 基因座的肿瘤相比，miR-17-92 簇的六个成员（除 miR-18a 外）在具有 miR-17-92 基因座获得的结直肠肿瘤中均显示出表达显着增加。无监督聚类分析根据 miR-17-92 位点增益的存在对肿瘤进行聚类。还发现 c-myc 的表达与 6 种 miRNA 之间存在显着相关性。在结直肠腺瘤向腺癌进展过程中，miR-17-92 簇的表达增加与 13q31 和 c-myc 表达上 miR17-92 位点的 DNA 拷贝数增加相关。
MicroRNAs are small non-coding RNA molecules, which regulate central mechanisms of tumorigenesis. In colorectal tumours, the combination of gain of 8q and 13q is one of the major factors associated with colorectal adenoma to adenocarcinoma progression. Functional studies on the miR-17-92 cluster localised on 13q31 have shown that its transcription is activated by c-myc, located on 8q, and that it has oncogenic activities. We investigated the contribution of the miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression. Expression levels of the miR-17-92 cluster were determined in 55 colorectal tumours and in 10 controls by real-time RT–PCR. Messenger RNA c-myc expression was also determined by real-time RT–PCR in 48 tumours with array comparative genomic hybridisation (aCGH) data available. From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain. Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain. Significant correlation between the expression of c-myc and the six miRNAs was also found. Increased expression of miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression is associated to DNA copy number gain of miR17-92 locus on 13q31 and c-myc expression.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
64.8
作者：
O'Donnell, KA;Wentzel, EA;Mendell, JT
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Mendell, JT
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64.8
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Reinhart, BJ;Slack, FJ;Ruvkun, G
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Ruvkun, G
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37.3
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Bandrés E;Cubedo E;Agirre X;Malumbres R;Zárate R;Ramirez N;Abajo A;Navarro A;Moreno I;Monzó M;García-Foncillas J
通讯作者：
García-Foncillas J
影响因子：
30.8
作者：
Chang, Tsung-Cheng;Yu, Duonan;Mendell, Joshua T.
通讯作者：
Mendell, Joshua T.