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miR-34c is down regulated in prostate cancer and exerts tumor suppressive functions.

Hagman, Zandra LU ; Larne, Olivia LU ; Edsjö, Anders LU ; Bjartell, Anders LU ; Ehrnström, Roy LU ; Ulmert, David LU ; Lilja, Hans LU and Ceder, Yvonne LU (2010) In International Journal of Cancer 127(12). p.2768-2776
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. There have been several reports of miRNA deregulation in prostate cancer and the biological evidence for an involvement of miRNAs in prostate tumorigenesis is increasing. In this study, we show that miR-34c is downregulated in prostate cancer (p = 0.0005) by performing qRT-PCR on 49 TURPs from prostate cancer patients compared to 25 from patients with benign prostatic hyperplasia. The miR-34c expression was found to inversely correlate to aggressiveness of the tumour, WHO grade, PSA levels and occurrence of metastases. Furthermore, a Kaplan-Meier analysis of patient survival based on miR-34c expression levels divided into low (<50(th)... (More)
MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. There have been several reports of miRNA deregulation in prostate cancer and the biological evidence for an involvement of miRNAs in prostate tumorigenesis is increasing. In this study, we show that miR-34c is downregulated in prostate cancer (p = 0.0005) by performing qRT-PCR on 49 TURPs from prostate cancer patients compared to 25 from patients with benign prostatic hyperplasia. The miR-34c expression was found to inversely correlate to aggressiveness of the tumour, WHO grade, PSA levels and occurrence of metastases. Furthermore, a Kaplan-Meier analysis of patient survival based on miR-34c expression levels divided into low (<50(th) percentile) and high (> 50(th) percentile) expression, significantly divides the patients into high risk and low risk patients (p = 0.0003, long-rank test). The phenotypic effects of miR-34c deregulation were studied in prostate cell lines, where ectopic expression of miR-34c decreased cell growth, due to both a decrease in cellular proliferation rate and an increase in apoptosis. In concordance to this, miR-34c was found to negatively regulate the oncogenes E2F3 and BCL-2, which stimulates proliferation and suppress apoptosis in prostate cancer cells respectively. Reversely, we could also show that blocking miR-34c in vitro increases cell growth. Further, ectopic expression of miR-34c was found to suppress migration and invasion. Our findings provide new insight into the role of miR-34c in the prostate, exhibiting tumor suppressing effects on proliferation, apoptosis and invasiveness. (c) 2010 UICC. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Cancer
volume
127
issue
12
pages
2768 - 2776
publisher
John Wiley & Sons
external identifiers
  • wos:000284208400004
  • pmid:21351256
  • scopus:78249234164
ISSN
0020-7136
DOI
10.1002/ijc.25269
language
English
LU publication?
yes
id
52ae1bb3-966e-4878-a720-9e7c220e40a0 (old id 1552585)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20162671?dopt=Abstract
date added to LUP
2010-03-03 14:28:06
date last changed
2018-06-17 03:09:39
@article{52ae1bb3-966e-4878-a720-9e7c220e40a0,
  abstract     = {MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. There have been several reports of miRNA deregulation in prostate cancer and the biological evidence for an involvement of miRNAs in prostate tumorigenesis is increasing. In this study, we show that miR-34c is downregulated in prostate cancer (p = 0.0005) by performing qRT-PCR on 49 TURPs from prostate cancer patients compared to 25 from patients with benign prostatic hyperplasia. The miR-34c expression was found to inversely correlate to aggressiveness of the tumour, WHO grade, PSA levels and occurrence of metastases. Furthermore, a Kaplan-Meier analysis of patient survival based on miR-34c expression levels divided into low (&lt;50(th) percentile) and high (&gt; 50(th) percentile) expression, significantly divides the patients into high risk and low risk patients (p = 0.0003, long-rank test). The phenotypic effects of miR-34c deregulation were studied in prostate cell lines, where ectopic expression of miR-34c decreased cell growth, due to both a decrease in cellular proliferation rate and an increase in apoptosis. In concordance to this, miR-34c was found to negatively regulate the oncogenes E2F3 and BCL-2, which stimulates proliferation and suppress apoptosis in prostate cancer cells respectively. Reversely, we could also show that blocking miR-34c in vitro increases cell growth. Further, ectopic expression of miR-34c was found to suppress migration and invasion. Our findings provide new insight into the role of miR-34c in the prostate, exhibiting tumor suppressing effects on proliferation, apoptosis and invasiveness. (c) 2010 UICC.},
  author       = {Hagman, Zandra and Larne, Olivia and Edsjö, Anders and Bjartell, Anders and Ehrnström, Roy and Ulmert, David and Lilja, Hans and Ceder, Yvonne},
  issn         = {0020-7136},
  language     = {eng},
  number       = {12},
  pages        = {2768--2776},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {miR-34c is down regulated in prostate cancer and exerts tumor suppressive functions.},
  url          = {http://dx.doi.org/10.1002/ijc.25269},
  volume       = {127},
  year         = {2010},
}