A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells.
A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells.
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DOI：
10.4161/cbt.8.21.9685
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发表时间：
2009-11
影响因子：
3.6
通讯作者：
Mendell JT
中科院分区：
文献类型：
--
作者：
Kent OA;Mullendore M;Wentzel EA;López-Romero P;Tan AC;Alvarez H;West K;Ochs MF;Hidalgo M;Arking DE;Maitra A;Mendell JT
microRNAs（miRNAs）是一类由21-24个核苷酸组成的RNA分子，可调控靶信使RNA的翻译和稳定性。miRNA表达异常是多种癌症的共同特征。一些先前的研究已经对胰腺导管腺癌（PDAC）中的miRNA表达进行了分类，尽管没有出现统一的miRNA失调模式。为了澄清这些先前的发现以及为详细的功能分析奠定基础，我们对21个人类PDAC细胞系进行了全球miRNA表达谱分析，这是迄今为止研究最广泛的一组。总体而言，与对照非转化胰腺导管细胞系相比，PDAC细胞系中有39种miRNA被发现失调，并且表达差异至少是对照非转化胰腺导管细胞系的两倍或更大。这些miRNAs中的几种在第一代患者来源的异种移植物中显示出相当的失调。初步功能分析表明，来自miR-200家族和miR-17-92簇的miRNA的强制表达增强了增殖，这两种miRNA在PDAC细胞系中均过表达。相反，抑制miR-200家族、miR-17-92簇或miR-191会减少锚定非依赖性生长。与已知的miR-200家族在负调节上皮-间充质转化（EMT）中的作用一致，这些miRNA的丰度与E-钙粘蛋白表达呈正相关，与EMT相关转录因子和已建立的miR-200靶点ZEB 1呈负相关。最后，miR-34 a（一种其表达在PDAC细胞系中经常丢失的miRNA）的恢复表达消除了生长，表明该miRNA的抗增殖活性在PDAC中起作用。这些结果，以及PDAC细胞系的广泛可用性，其中产生上述数据，为胰腺癌研究界提供了宝贵的资源，并将极大地促进功能研究，阐明胰腺癌中miRNA失调的后果。
MicroRNAs (miRNAs) are 21-24 nucleotide RNA molecules that regulate the translation and stability of target messenger RNAs. Abnormal miRNA expression is a common feature of diverse cancers. Several previous studies have classified miRNA expression in pancreatic ductal adenocarcinoma (PDAC), although no uniform pattern of miRNA dysregulation has emerged. To clarify these previous findings as well as to set the stage for detailed functional analyses, we performed global miRNA expression profiling of 21 human PDAC cell lines, the most extensive panel studied to date. Overall, 39 miRNAs were found to be dysregulated and have at least two-fold or greater differential expression in PDAC cell lines compared to control non-transformed pancreatic ductal cell lines. Several of these miRNAs show comparable dysregulation in first-passage patient-derived xenografts. Initial functional analyses demonstrate that enforced expression of miRNAs derived from the miR-200 family and the miR-17-92 cluster, both of which are overexpressed in PDAC cell lines, enhances proliferation. In contrast, inhibition of the miR-200 family, the miR-17-92 cluster, or miR-191 diminishes anchorage independent growth. Consistent with a known role for the miR-200 family in negatively regulating an epithelial-to-mesenchymal transition (EMT), the abundance of these miRNAs correlated positively with E-cadherin expression and negatively with the EMT-associated transcription factor and established miR-200 target ZEB1. Finally, restituted expression of miR-34a, a miRNA whose expression is frequently lost in PDAC cell lines, abrogates growth, demonstrating that the anti-proliferative activity of this miRNA is operative in PDAC. These results, and the widespread availability of PDAC cell lines wherein the aforementioned data were generated, provide a valuable resource for the pancreatic cancer research community and will greatly facilitate functional studies essential for elucidating the consequences of miRNA dysregulation in pancreatic cancer.
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影响因子：
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作者：
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