Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c
Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c
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DOI：
10.1002/path.2437
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发表时间：
2008-12-01
影响因子：
7.3
通讯作者：
Moriyama, M.
中科院分区：
文献类型：
--
作者：
Nakada, C.;Matsuura, K.;Moriyama, M.
我们利用microRNA微阵列平台研究了肾细胞癌[透明细胞癌（CCC）和嫌色肾细胞癌（ChCC）]和正常肾脏中microRNA （miRNA）的表达谱，该平台共包含470种人类miRNA （Sanger miRBase release 9.1）。无监督聚类分析表明，CCC和ChCC是可分离的，CCCs中没有亚群。我们发现43个mirna在CCC与正常肾脏之间存在差异表达，其中37个在CCC中显著下调，6个在CCC中上调。我们还发现，57个mirna在ChCC与正常肾脏之间存在差异表达，其中51个在ChCC中显著下调，6个在ChCC中上调。总之，这些观察结果表明，与正常肾脏相比，CCC和ChCC中mirna的表达倾向于下调。我们观察到，miR-141和miR-200c是CCCs中下调最显著的mirna。事实上，在分析的所有CCC病例中，与正常肾脏相比，miR-141和miR-200c均下调。微阵列数据和定量RT-PCR显示，这两个mirna的表达是一致的。TargetScan算法显示ZFHX1B mRNA是miR-141和-200c的假设靶标。我们通过定量RT-PCR证实，在miR-141和miR-200c下调的CCCs中，CDH1/E-cadherin的转录抑制因子ZFHX1B倾向于上调。此外，我们发现miR-141和miR-200c过表达导致两种肾癌细胞系ACHN和786-O中ZFHX1B下调和E-cadherin上调。基于这些发现，我们认为CCCs中miR-141和miR-200c的下调可能通过上调ZFHX1B参与了CDH1/E-cadherin转录的抑制。版权所有2008年英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
We investigated expression profiles of microRNA (miRNA) in renal cell carcinoma [clear cell carcinomas (CCC) and chromophobe renal cell carcinomas (ChCC)] and in normal kidneys by using a miRNA microarray platform which covers a total of 470 human miRNAs (Sanger miRBase release 9.1). Unsupervised hierarchical cluster analysis revealed that CCC and ChCC were separable and that no subgroups were identified in CCCs. We found that 43 miRNAs were differentially expressed between CCC and normal kidney, of which 37 were significantly down-regulated in CCC and the other 6 were up-regulated. We also found that 57 miRNAs were differentially expressed between ChCC and normal kidney, of which 51 were significantly down-regulated in ChCC and the other 6 were up-regulated. Together, these observations indicate that expression of miRNAs tends to be down-regulated in both CCC and ChCC compared with normal kidney. We observed that miR-141 and miR-200c were the most significantly down-regulated miRNAs in CCCs. Indeed, in all cases of CCC analysed, both miR-141 and miR-200c were down-regulated in comparison with normal kidney. Microarray data and quantitative RT-PCR showed that these two miRNAs were expressed concordantly. TargetScan algorithm revealed that ZFHX1B mRNA is a hypothetical target of both miR-141 and -200c. We established by quantitative RT-PCR that, in CCCs in which miR-141 and miR-200c were down-regulated, ZFHX1B, a transcriptional repressor for CDH1/E-cadherin, tended to be up-regulated. Furthermore, we found that overexpression of miR-141 and miR-200c caused down-regulation of ZFHX1B and upregulation of E-cadherin in two renal carcinoma cell lines, ACHN and 786-O. On the basis of these findings, we suggest that down-regulation of miR-141 and miR-200c in CCCs might be involved in suppression of CDH1/E-cadherin transcription via up-regulation of ZFHX1B. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.