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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4006071
- author
- Hagman, Zandra
LU
; Haflidadottir, Benedikta
LU
; Ansari, Mahreen
LU
; Persson, Margareta
LU
; Bjartell, Anders
LU
; Edsjö, Anders
LU
and Ceder, Yvonne
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- British Journal of Cancer
- volume
- 109
- issue
- 5
- pages
- 8 pages
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Molecular Medicine (013031200), Division of Urological Cancers (013243420), Clinical Chemistry, Malmö (013016000)
- 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
- 2016-04-01 09:50:51
- date last changed
- 2022-05-19 02:19:58
@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 = {{https://lup.lub.lu.se/search/files/1313662/4316504.pdf}},
doi = {{10.1038/bjc.2013.449}},
volume = {{109}},
year = {{2013}},
}