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Downregulation of miR-92a Is Associated with Aggressive Breast Cancer Features and Increased Tumour Macrophage Infiltration.

Björner, Sofie LU ; Möller, Christina LU ; Jirström, Karin LU ; Lee, Alexander; Busch, Susann; Lamb, Rebecca and Landberg, Göran LU (2012) In PLoS ONE 7(4).
Abstract
BACKGROUND:

MicroRNAs are small non-coding RNAs involved in the regulation of gene expression on a posttranscriptional level. These regulatory RNAs have been implicated in numerous cellular processes and are further deregulated in different cancer types, including breast cancer. MiR-92a is part of the miR-17∼92 cluster, which was first reported to be linked to tumourigenesis. However, little is known about the expression of miR-92a in breast cancer and potential associations to tumour properties. The expression of miR-92a was therefore characterized in 144 invasive breast cancer samples using in situ hybridization and related to clinico-pathological data as well as to selected key properties of the tumour stroma, including the... (More)
BACKGROUND:

MicroRNAs are small non-coding RNAs involved in the regulation of gene expression on a posttranscriptional level. These regulatory RNAs have been implicated in numerous cellular processes and are further deregulated in different cancer types, including breast cancer. MiR-92a is part of the miR-17∼92 cluster, which was first reported to be linked to tumourigenesis. However, little is known about the expression of miR-92a in breast cancer and potential associations to tumour properties. The expression of miR-92a was therefore characterized in 144 invasive breast cancer samples using in situ hybridization and related to clinico-pathological data as well as to selected key properties of the tumour stroma, including the presence of macrophages (CD68) and cancer activated fibroblasts (alpha-SMA).



METHODOLOGY/PRINCIPAL FINDINGS:

To measure miR-92a levels, an in situ hybridisation protocol was developed and validated using cell lines and miR-92a inhibitors. The expression in the tumour samples was objectively evaluated using digital image analysis program subtracting background activities. We found that the miR-92a expression varied between tumours and was inversely correlated to tumour grade (r = -0.276, p = 0.003) and recurrence-free survival (p = 0.008) and provided independent prognostic information in multivariate Cox analysis (HR: 0.375, CI: 0.145-0.972, p = 0.043). MiR-92a was moreover inversely correlated to the number of infiltrating macrophages in the tumour stroma (r = -0.357, p<0.001), and downregulation of miR-92a promoted cell migration (p<0.01).



CONCLUSIONS/SIGNIFICANCE:

This study demonstrates that downregulation of miR-92a in breast cancer is linked to key epithelial and stromal properties as well as clinical outcome. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
7
issue
4
publisher
Public Library of Science
external identifiers
  • wos:000305349100064
  • pmid:22563438
  • scopus:84860370107
ISSN
1932-6203
DOI
10.1371/journal.pone.0036051
language
English
LU publication?
yes
id
81e94272-cc77-4c80-93b7-fa43fc6bba1b (old id 2609066)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22563438?dopt=Abstract
date added to LUP
2012-06-02 16:28:09
date last changed
2017-11-19 04:01:19
@article{81e94272-cc77-4c80-93b7-fa43fc6bba1b,
  abstract     = {BACKGROUND:<br/><br>
MicroRNAs are small non-coding RNAs involved in the regulation of gene expression on a posttranscriptional level. These regulatory RNAs have been implicated in numerous cellular processes and are further deregulated in different cancer types, including breast cancer. MiR-92a is part of the miR-17∼92 cluster, which was first reported to be linked to tumourigenesis. However, little is known about the expression of miR-92a in breast cancer and potential associations to tumour properties. The expression of miR-92a was therefore characterized in 144 invasive breast cancer samples using in situ hybridization and related to clinico-pathological data as well as to selected key properties of the tumour stroma, including the presence of macrophages (CD68) and cancer activated fibroblasts (alpha-SMA).<br/><br>
<br/><br>
METHODOLOGY/PRINCIPAL FINDINGS:<br/><br>
To measure miR-92a levels, an in situ hybridisation protocol was developed and validated using cell lines and miR-92a inhibitors. The expression in the tumour samples was objectively evaluated using digital image analysis program subtracting background activities. We found that the miR-92a expression varied between tumours and was inversely correlated to tumour grade (r = -0.276, p = 0.003) and recurrence-free survival (p = 0.008) and provided independent prognostic information in multivariate Cox analysis (HR: 0.375, CI: 0.145-0.972, p = 0.043). MiR-92a was moreover inversely correlated to the number of infiltrating macrophages in the tumour stroma (r = -0.357, p&lt;0.001), and downregulation of miR-92a promoted cell migration (p&lt;0.01).<br/><br>
<br/><br>
CONCLUSIONS/SIGNIFICANCE:<br/><br>
This study demonstrates that downregulation of miR-92a in breast cancer is linked to key epithelial and stromal properties as well as clinical outcome.},
  articleno    = {e36051},
  author       = {Björner, Sofie and Möller, Christina and Jirström, Karin and Lee, Alexander and Busch, Susann and Lamb, Rebecca and Landberg, Göran},
  issn         = {1932-6203},
  language     = {eng},
  number       = {4},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Downregulation of miR-92a Is Associated with Aggressive Breast Cancer Features and Increased Tumour Macrophage Infiltration.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0036051},
  volume       = {7},
  year         = {2012},
}