MicroRNA-145 targets YES and STAT1 in colon cancer cells

Lea H Gregersen; Anders B Jacobsen; Lisa Frankel; Jiayu Wen; Anders Krogh; Anders H. Lund

doi:10.1371/journal.pone.0008836

MicroRNA-145 targets YES and STAT1 in colon cancer cells

Lea H Gregersen, Anders B Jacobsen, Lisa Frankel, Jiayu Wen, Anders Krogh, Anders H. Lund

149 Citations (Scopus)

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Abstract

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.

Original language	English
Journal	PLoS ONE
Volume	5
Issue number	1
Pages (from-to)	e8836
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0008836
Publication status	Published - 21 Jan 2010

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title = "MicroRNA-145 targets YES and STAT1 in colon cancer cells",

abstract = "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.",

author = "Gregersen, {Lea H} and Jacobsen, {Anders B} and Lisa Frankel and Jiayu Wen and Anders Krogh and Lund, {Anders H.}",

note = "KeyWords Plus: COLORECTAL-CANCER; SUPPRESSIVE MICRORNAS; PROSTATE-CANCER; MESSENGER-RNAS; EXPRESSION; GROWTH; CARCINOMA; SIGNATURES; MECHANISM; MIR-145",

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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

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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.

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JO - PLoS Computational Biology

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MicroRNA-145 targets YES and STAT1 in colon cancer cells

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