MicroRNA-145 targets YES and STAT1 in colon cancer cells.
BACKGROUND
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.


RESULTS
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
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.
Gregersen
Lea H
LH
Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
Jacobsen
Anders B
AB
Frankel
Lisa B
LB
Wen
Jiayu
J
Krogh
Anders
A
Lund
Anders H
AH
D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D051575:Proto-Oncogene Proteins c-yes / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics*
D020413:3' Untranslated Regions; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D051575:Proto-Oncogene Proteins c-yes; C489834:YES1 protein, human