CDKN2A, NF2, and JUN Are Dysregulated Among Other Genes by miRNAs in Malignant Mesothelioma-A miRNA Microarray Analysis
CDKN2A, NF2, and JUN Are Dysregulated Among Other Genes by miRNAs in Malignant Mesothelioma-A miRNA Microarray Analysis
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DOI：
10.1002/gcc.20669
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发表时间：
2009-07-01
影响因子：
3.7
通讯作者：
Knuutila, Sakari
中科院分区：
文献类型：
--
作者：
Guled, Mohamed;Lahti, Leo;Knuutila, Sakari
恶性间皮瘤（MM）是一种侵袭性的癌症，主要是由于以前接触石棉引起的间皮瘤细胞。目前对MM的microRNA（miRNA）表达知之甚少。miRNA是一种小的非编码RNA，在基因表达调控中起重要作用。本研究采用miRNA微阵列技术分析了17例MM患者的miRNA表达谱。该分析区分了肿瘤组织和正常间皮瘤的总体miRNA表达谱。与正常组织相比，肿瘤组织中存在差异表达的miRNAs。其中12个，let-7 b *、miR-1228*、miR-195*、miR-30 b *、miR-32*、miR-345、miR-483- 3 p、miR-584、miR-595、miR-615- 3 p和miR-885- 3 p高度表达，而其余9个，let-7 e *、miR-144*、miR-203、miR-340*、miR-34 a *、miR-423、miR-424、miR-425、miR-582、miR-7-1* 和miR-9未表达或表达水平严重降低。这些miRNA的靶基因包括MM中最常受影响的基因，如CDKN 2A、NF 2、JUN、HGF和PDGFA。许多miRNA位于MM中已知缺失或获得的染色体区域，如8 q24，Ip 36和14 q32。此外，我们可以确定特定的miRNAs为MM的每种组织病理学亚型。关于危险因素，如吸烟状态和石棉暴露，显着差异表达的miRNAs在吸烟者与非吸烟者（miR-379，miR-301 a，miR-299- 3 p，miR-455- 3 p，和miR-127- 3 p），但没有在石棉暴露患者与非暴露的。这可能与石棉暴露评估方法有关，因为石棉仍然是MM开发的主要贡献者。（C）2009 Wiley-Liss，Inc.
Malignant mesothelioma (MM) is an aggressive cancer arising from mesothelial cells, mainly due to former asbestos exposure. Little is known about the microRNA (miRNA) expression of MM. miRNAs are small noncoding RNAs, which play an essential role in the regulation of gene expression. This study was carried out to analyze the miRNA expression profile of 17 MM samples using miRNA microarray. The analysis distinguished the overall miRNA expression profiles of tumor tissue and normal mesothelium. Differentially expressed miRNAs were found in tumor samples compared with normal sample. Twelve of them, let-7b*, miR-1228*, miR-195*, miR-30b*, miR-32*, miR-345, miR-483-3p, miR-584, miR-595, miR-615-3p, and miR-885-3p, were highly expressed whereas the remaining nine, let-7e*, miR-144*, miR-203, miR-340*, miR-34a*, miR-423, miR-582, miR-7-1*, and miR-9, were unexpressed or had severely reduced expression levels. Target genes for these miRNAs include the most frequently affected genes in MM such as CDKN2A, NF2, JUN, HGF and PDGFA. Many of the miRNAs were located in chromosomal areas known to be deleted or gained in MM such as 8q24, Ip36, and 14q32. Furthermore, we could identify specific miRNAs for each histopathological subtype of MM. Regarding risk factors such as smoking status and asbestos exposure, significantly differentially expressed miRNAs were identified in smokers versus nonsmokers (miR-379, miR-301a, miR-299-3p, miR-455-3p, and miR-127-3p), but not in asbestos-exposed patients versus nonexposed ones. This could be related to the method of assessment of asbestos exposure as asbestos remains to be the main contributor to the development of MM. (C) 2009 Wiley-Liss, Inc.