MicroRNA-145 targets YES and STAT1 in colon cancer cells.
MicroRNA-145 targets YES and STAT1 in colon cancer cells.
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DOI：
10.1371/journal.pone.0008836
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发表时间：
2010-01-21
期刊：
影响因子：
3.7
通讯作者：
Lund AH
中科院分区：
文献类型：
--
作者：
Gregersen LH;Jacobsen AB;Frankel LB;Wen J;Krogh A;Lund AH
MicroRNAs(MiRNAs)已成为重要的基因调控因子，并被认为是肿瘤发生过程中的关键分子。据报道，MIR-145在几种癌症中表达下调，但对其在结肠癌中的靶点的了解仍然有限。为了研究miR-145在结肠癌中的作用，我们采用了一种基于微阵列的方法来识别miR-145靶点。基于种子位点浓缩分析和无偏向词语分析，我们发现在miRNA过表达下调的转录本的3‘-非翻译区(UTRs)上，miRNA结合位点显著丰富。基因本体论分析表明，与细胞死亡、细胞生长和增殖、细胞周期、基因表达和癌症有关的基因过度表达。许多已确定的miRNA靶点以前被认为与癌症有关，包括YES、FSCN1、ADAM17、BIRC2、VANGL1以及转录因子STAT1。YES和STAT1都被证实是miR-145的直接靶点。这项研究确定并验证了结肠癌细胞中miR-145与癌症相关的新的直接靶点，从而增加了对miR-145抑瘤功能的重要机制理解。
MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in tumorigenesis. miR-145 is reported to be down-regulated in several cancers, but knowledge of its targets in colon cancer remains limited. To investigate the role of miR-145 in colon cancer, we have employed a microarray based approach to identify miR-145 targets. Based on seed site enrichment analyses and unbiased word analyses, we found a significant enrichment of miRNA binding sites in the 3′-untranslated regions (UTRs) of transcripts down-regulated upon miRNA overexpression. Gene Ontology analysis showed an overrepresentation of genes involved in cell death, cellular growth and proliferation, cell cycle, gene expression and cancer. A number of the identified miRNA targets have previously been implicated in cancer, including YES, FSCN1, ADAM17, BIRC2, VANGL1 as well as the transcription factor STAT1. Both YES and STAT1 were verified as direct miR-145 targets. The study identifies and validates new cancer-relevant direct targets of miR-145 in colon cancer cells and hereby adds important mechanistic understanding of the tumor-suppressive functions of miR-145.
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