Expression profiling identifies microRNA signature in pancreatic cancer
Expression profiling identifies microRNA signature in pancreatic cancer
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DOI：
10.1002/ijc.22394
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发表时间：
2007-03-01
影响因子：
6.4
通讯作者：
Schmittgen, Thomas D.
中科院分区：
文献类型：
--
作者：
Lee, Eun Jon;Gusev, Yuriy;Schmittgen, Thomas D.
microRNA是负调控基因表达的功能性22 nt非编码RNA。microRNA表达的紊乱可能在某些疾病的发生和发展中起作用。已经鉴定出与胰腺癌相关的microRNA表达特征。这已经通过对人胰腺癌、配对良性组织、正常胰腺、慢性胰腺炎和9种胰腺癌细胞系的标本上的200多种microRNA前体的实时PCR分析来实现。系统聚类能够区分肿瘤与正常胰腺、胰腺炎和细胞系。PAM算法正确分类了28个肿瘤中的28个，6个正常胰腺中的6个和15个相邻良性组织中的11个。100种microRNA前体在胰腺癌或结缔组织增生中异常表达（p < 0.01），包括先前报道在其他人类癌症中差异表达的microRNA（miR-155、miR-21、miR-221和miR-222）以及先前未报道在癌症中差异表达的microRNA（miR-376 a和miR-301）。大多数异常表达的miRNA在肿瘤中表现出表达增加。使用实时PCR测定来定量成熟microRNA和北方印迹来验证活性成熟microRNA的表达。逆转录原位PCR结果显示，差异表达最高的3种miRNAs（miR-221、-376a和-301）定位于肿瘤细胞，而不定位于间质或正常腺泡或导管。microRNA的异常表达可能为胰腺肿瘤的发生提供新的线索，并可能为胰腺癌的诊断提供生物标志物。(c)2006威利-利斯公司
microRNAs are functional, 22 nt, noncoding RNAs that negatively regulate gene expression. Disturbance of microRNA expression may play a role in the initiation and progression of certain diseases. A microRNA expression signature has been identified that is associated with pancreatic cancer. This has been accomplished with the application of real-time PCR profiling of over 200 microRNA precursors on specimens of human pancreatic adenocarcinoma, paired benign tissue, normal pancreas, chronic pancreatitis and nine pancreatic cancer cell lines. Hierarchical clustering was able to distinguish tumor from normal pancreas, pancreatitis and cell lines. The PAM algorithm correctly classified 28 of 28 tumors, 6 of 6 normal pancreas and 11 of 15 adjacent benign tissues. One hundred microRNA precursors were aberrantly expressed in pancreatic cancer or desmoplasia (p < 0.01), including microRNAs previously reported as differentially expressed in other human cancers (miR-155, miR21, miR-221 and miR-222) as well as those not previously reported in cancer (miR-376a and miR-301). Most of the top aberrantly expressed miRNAs displayed increased expression in the tumor. Expression of the active, mature microRNA was validated using a real-time PCR assay to quantify the mature microRNA and Northern blotting. Reverse transcription in situ PCR showed that three of the top differentially expressed miRNAs (miR-221, -376a and -301) were localized to tumor cells and not to stroma or normal acini or ducts. Aberrant microRNA expression may offer new clues to pancreatic tumorigenesis and may provide diagnostic biomarkers for pancreatic adenocarcinoma. (c) 2006 Wiley-Liss, Inc.