MicroRNAs and their target messenger RNAs associated with endometrial carcinogenesis
MicroRNAs and their target messenger RNAs associated with endometrial carcinogenesis
复制标题
DOI：
10.1016/j.ygyno.2008.03.023
复制
发表时间：
2008-08-01
影响因子：
4.7
通讯作者：
Lancaster, Johnathan M.
中科院分区：
文献类型：
--
作者：
Boren, Todd;Xiong, Yin;Lancaster, Johnathan M.
Objective.基因表达技术的最新进展提供了与子宫内膜癌发展相关的全球信使RNA（mRNA）表达变化的见解。然而，转录后事件，也可能有表型的后果仍然是完全划定。微小RNA（microRNAs，miRNAs）是一类小的非编码RNA转录物，通过调节多个靶mRNA基因的转录后活性来影响细胞功能。虽然最近的报道表明miRNAs可能影响人类癌症的发展，但其在子宫内膜癌发生中的作用仍有待描述。我们检测了61例新鲜冷冻子宫内膜标本中335种独特的人类miRNAs的表达，其中包括37例子宫内膜癌，20例正常子宫内膜和4例复杂的不典型增生样本。平行地，使用Affyssin Human U133 A基因芯片分析29个子宫内膜样本中22，000个mRNA基因的表达，包括20个子宫内膜癌和9个正常子宫内膜样本。整合差异表达的mRNA、miRNA和预测的miRNA-mRNA靶点，并评估其相关功能生物学途径的代表性。13种miRNAs（p < 0.02）和90种mRNAs（FDR; 0%）被鉴定为与子宫内膜癌的发展相关。90个差异表达的mRNA中有26个（29%）是Sangar数据库预测的13个miRNA的mRNA靶。通路分析表明这26个mRNA基因在细胞死亡、生长、增殖和癌变过程中起重要作用。我们已经鉴定了与子宫内膜癌发展相关的miRNAs和mRNAs。此外，我们整合miRNA/mRNA数据的策略也可能有助于识别重要的生物学途径和在子宫内膜发病机制中具有重要意义的其他独特基因。(c)2008年爱思唯尔公司All rights reserved.
Objective. Recent advances in gene expression technology have provided insights into global messenger RNA (mRNA) expression changes associated with endometrial cancer development. However, the post-transcriptional events that may also have phenotypic consequences remain to be completely delineated. MicroRNAs (miRNAs) are small non-coding RNA transcripts, that influence cell function via modulation of post-transcriptional activity of multiple target mRNA genes. Although recent reports suggest that miRNAs may influence human cancer development, their role in endometrial carcinogenesis remains to be described.Methods. We measured expression of 335 unique human miRNAs in 61 fresh-frozen endometrial specimens, including 37 endometrial cancers, 20 normal endometrium, and 4 complex atypical hyperplasia samples. In parallel, expression of 22,000 mRNA genes was analyzed using the Affymetrix Human U133A GeneChips in 29 of the endometrial samples, including 20 endometrial carcinomas and 9 normal endometrial samples. Differentially expressed mRNAs, miRNAs, and predicted miRNA-mRNA targets were integrated and evaluated for representation of relevant functional biologic pathways.Results. Thirteen miRNAs (p < 0.02) and 90 mRNAs (FDR; 0%) were identified to be associated with endometrial cancer development. Twenty-six of the 90 (29%) differentially expressed mRNAs are Sangar-database predicted mRNA targets of the 13 miRNAs. Pathway analysis demonstrates significant involvement of these 26 mRNA genes in processes including cell death, growth, proliferation, and carcinogenesis.Conclusion. We have identified miRNAs and mRNAs associated with endometrial cancer development. Further, our strategy of integrating miRNA/mRNA data may also aid in the identification of important biologic pathways and additional unique genes that have importance in endometrial pathogenesis. (c) 2008 Elsevier Inc. All rights reserved.