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The tumour suppressor miR-34c targets MET in prostate cancer cells.

Hagman, Zandra LU ; Haflidadottir, Benedikta LU ; Ansari, Mahreen LU ; Persson, Margareta LU ; Bjartell, Anders LU ; Edsjö, Anders LU and Ceder, Yvonne LU (2013) In British Journal of Cancer 109(5). p.1271-1278
Abstract
Background:The microRNA, miR-34c, is a well-established regulator of tumour suppression. It is downregulated in most forms of cancers and inhibits malignant growth by repressing genes involved in processes such as proliferation, anti-apoptosis, stemness, and migration. We have previously reported downregulation and tumour suppressive properties for miR-34c in prostate cancer (PCa).Methods:In this study, we set out to further characterize the mechanisms by which miR-34c deregulation contributes to PCa progression. The genes regulated by miR-34c in the PCa cell line PC3 were identified by microarray analyses and were found to be enriched in cell death, cell cycle, cellular growth, and cellular movement pathways. One of the identified targets... (More)
Background:The microRNA, miR-34c, is a well-established regulator of tumour suppression. It is downregulated in most forms of cancers and inhibits malignant growth by repressing genes involved in processes such as proliferation, anti-apoptosis, stemness, and migration. We have previously reported downregulation and tumour suppressive properties for miR-34c in prostate cancer (PCa).Methods:In this study, we set out to further characterize the mechanisms by which miR-34c deregulation contributes to PCa progression. The genes regulated by miR-34c in the PCa cell line PC3 were identified by microarray analyses and were found to be enriched in cell death, cell cycle, cellular growth, and cellular movement pathways. One of the identified targets was MET, a receptor tyrosine kinase activated by hepatocyte growth factor, that is crucial for metastatic progression.Results:We confirmed the inhibitory effect of miR-34c on both MET transcript and protein levels. The binding of miR-34c to two binding sites in the 3'-UTR of MET was validated using luciferase reporter assays and target site blockers. The effect of this regulation on the miR-34c inhibition of the migratory phenotype was also confirmed. In addition, a significant inverse correlation between miR-34c expression levels and MET immunostaining was found in PCa patients.Conclusion:These findings provide a novel molecular mechanism of MET regulation in PCa and contribute to the increasing evidence that miR-34c has a key tumour suppressive role in PCa.British Journal of Cancer advance online publication, 6 August 2013; doi:10.1038/bjc.2013.449 www.bjcancer.com. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
British Journal of Cancer
volume
109
issue
5
pages
1271 - 1278
publisher
Nature Publishing Group
external identifiers
  • wos:000324168500024
  • pmid:23922103
  • scopus:84883741072
ISSN
1532-1827
DOI
10.1038/bjc.2013.449
language
English
LU publication?
yes
id
b5142d30-a5ce-4ad9-9104-962156b5423c (old id 4006071)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23922103?dopt=Abstract
date added to LUP
2013-09-03 14:23:37
date last changed
2019-09-17 01:01:30
@article{b5142d30-a5ce-4ad9-9104-962156b5423c,
  abstract     = {Background:The microRNA, miR-34c, is a well-established regulator of tumour suppression. It is downregulated in most forms of cancers and inhibits malignant growth by repressing genes involved in processes such as proliferation, anti-apoptosis, stemness, and migration. We have previously reported downregulation and tumour suppressive properties for miR-34c in prostate cancer (PCa).Methods:In this study, we set out to further characterize the mechanisms by which miR-34c deregulation contributes to PCa progression. The genes regulated by miR-34c in the PCa cell line PC3 were identified by microarray analyses and were found to be enriched in cell death, cell cycle, cellular growth, and cellular movement pathways. One of the identified targets was MET, a receptor tyrosine kinase activated by hepatocyte growth factor, that is crucial for metastatic progression.Results:We confirmed the inhibitory effect of miR-34c on both MET transcript and protein levels. The binding of miR-34c to two binding sites in the 3'-UTR of MET was validated using luciferase reporter assays and target site blockers. The effect of this regulation on the miR-34c inhibition of the migratory phenotype was also confirmed. In addition, a significant inverse correlation between miR-34c expression levels and MET immunostaining was found in PCa patients.Conclusion:These findings provide a novel molecular mechanism of MET regulation in PCa and contribute to the increasing evidence that miR-34c has a key tumour suppressive role in PCa.British Journal of Cancer advance online publication, 6 August 2013; doi:10.1038/bjc.2013.449 www.bjcancer.com.},
  author       = {Hagman, Zandra and Haflidadottir, Benedikta and Ansari, Mahreen and Persson, Margareta and Bjartell, Anders and Edsjö, Anders and Ceder, Yvonne},
  issn         = {1532-1827},
  language     = {eng},
  number       = {5},
  pages        = {1271--1278},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {The tumour suppressor miR-34c targets MET in prostate cancer cells.},
  url          = {http://dx.doi.org/10.1038/bjc.2013.449},
  volume       = {109},
  year         = {2013},
}