Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
PLoS One. 2010 Jan 21;5(1):e8836. doi: 10.1371/journal.pone.0008836.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSIONS/SIGNIFICANCE: 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.
MicroRNAs（miRNAs）已成为重要的基因调控因子，被认为是肿瘤发生的关键因素。已有报道称 miR-145 在几种癌症中下调，但结肠癌中其靶标的知识仍然有限。
方法/主要发现：为了研究 miR-145 在结肠癌中的作用，我们采用了基于微阵列的方法来鉴定 miR-145 的靶标。基于种子序列富集分析和无偏词分析，我们发现 miRNA 过表达时下调的转录物的 3'-非翻译区（UTR）中有大量 miRNA 结合位点富集。基因本体论分析显示，细胞死亡、细胞生长和增殖、细胞周期、基因表达和癌症相关基因的表达明显增加。鉴定出的一些 miRNA 靶标先前已被涉及癌症，包括 YES、FSCN1、ADAM17、BIRC2、VANGL1 以及转录因子 STAT1。YES 和 STAT1 都被验证为 miR-145 的直接靶标。
结论/意义：本研究鉴定并验证了 miR-145 在结肠癌细胞中的新的癌症相关直接靶标，为 miR-145 的肿瘤抑制功能提供了重要的机制理解。
