Association of microRNA-21 expression with its targets, PDCD4 and TIMP3, in pancreatic ductal adenocarcinoma
Association of microRNA-21 expression with its targets, PDCD4 and TIMP3, in pancreatic ductal adenocarcinoma
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DOI：
10.1038/modpathol.2011.142
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发表时间：
2012-01-01
期刊：
影响因子：
7.5
通讯作者：
Hashimoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Nagao, Yuichi;Hisaoka, Masanori;Hashimoto, Hiroshi
自从发现小的非编码RNA以来，对微小RNA(MiRNA)在人类癌症中的表达模式的分析为癌症生物学提供了新的见解。MiRNA-21被认为是在包括胰腺癌在内的多种恶性肿瘤的发生或生物学行为中发挥重要作用的miRNA之一。本研究旨在探讨胰腺癌组织中miRNA-21的表达与其分子靶标细胞程序性死亡4(PDCD4)和金属蛋白酶组织抑制因子3(TIMP3)表达的关系。本研究以65例胰腺导管腺癌和5例正常胰腺组织为对照。利用微阵列平台对5例胰腺导管腺癌和5例正常胰腺组织的miRNA表达谱进行了分析，并进行了等级聚类分析。用实时定量逆转录聚合酶链式反应(RT-PCR)进一步检测65例胰腺导管腺癌中最高表达的miRNA。应用免疫组织化学方法检测其分子靶点(如PDCD4、TIMP3)在胰腺导管腺癌中的表达。在芯片分析中，与正常胰腺组织相比，28个miRNAs在胰腺导管腺癌组织中上调，而48个miRNAs下调。在所分析的胰腺导管腺癌中，miRNA-21是最显著的过表达的miRNA，在实时定量RT-PCR检测的65例胰腺导管腺癌中，也有75%的病例高表达。在胰腺导管腺癌患者中，miRNA21高表达与预后不良相关(P=0.045)。PDCD4(核染色减少)和TIMP3(下调表达)的免疫组织化学表达模式与miR-21表达上调显著相关(P
Since the discovery of small non-coding RNAs, the analyses of microRNA (miRNA) expression patterns in human cancer have provided new insights into cancer biology. miRNA-21 has been suggested to be one of the miRNAs that have an important role in the development or biological behavior of a variety of malignancies, including pancreatic cancer. This study was conducted to evaluate the relationship between the expression of miRNA-21 and that of its molecular targets, programmed cell death 4 (PDCD4) and tissue inhibitor of metalloproteinase (TIMP3), in pancreatic ductal adenocarcinoma. The study included 65 pancreatic ductal adenocarcinomas and 5 normal pancreatic tissue specimens for comparison. The miRNA expression profiling of five selected pancreatic ductal adenocarcinomas and five normal pancreatic specimens was performed using a microarray platform, and was evaluated by a hierarchical clustering analysis. The miRNA most highly expressed in pancreatic ductal adenocarcinomas (ie, miRNA-21) was further assessed by quantitative real-time reverse transcription PCR (RT-PCR) assays in the 65 pancreatic ductal adenocarcinoma cases. The expression pattern of its molecular targets (eg, PDCD4 and TIMP3) in pancreatic ductal adenocarcinoma was examined immunohistochemically. In the microarray analyses, 28 miRNAs were upregulated in pancreatic ductal adenocarcinoma compared with normal pancreatic tissue, whereas 48 miRNAs were downregulated. miRNA-21 was the most significantly overexpressed miRNA in the pancreatic ductal adenocarcinomas analyzed, and was also highly expressed in 75% of the 65 pancreatic ductal adenocarcinomas examined by real-time RT-PCR. High miRNA-21 expression was correlated with a worse prognosis in the pancreatic ductal adenocarcinoma patients (P=0.045). The immunohistochemical expression patterns of PDCD4 (reduced nuclear staining pattern) and TIMP3 (downregulated expression) were significantly associated with both the upregulated miR-21 expression (P