TY - JOUR
T1 - MicroRNA-145 targets YES and STAT1 in colon cancer cells
AU - Gregersen, Lea H
AU - Jacobsen, Anders B
AU - Frankel, Lisa
AU - Wen, Jiayu
AU - Krogh, Anders
AU - Lund, Anders H.
N1 - KeyWords Plus: COLORECTAL-CANCER; SUPPRESSIVE MICRORNAS; PROSTATE-CANCER; MESSENGER-RNAS; EXPRESSION; GROWTH; CARCINOMA; SIGNATURES; MECHANISM; MIR-145
PY - 2010/1/21
Y1 - 2010/1/21
N2 - 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. 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 39-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.
AB - 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. 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 39-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.
U2 - 10.1371/journal.pone.0008836
DO - 10.1371/journal.pone.0008836
M3 - Journal article
C2 - 20098684
SN - 1932-6203
VL - 5
SP - e8836
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 1
ER -
