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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 orcid ; 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
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
7
issue
4
article number
e36051
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000305349100064
  • pmid:22563438
  • scopus:84860370107
  • pmid:22563438
ISSN
1932-6203
DOI
10.1371/journal.pone.0036051
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: Pathology, (Lund) (013030000), Pathology (Malmö) (013031000)
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
2016-04-01 14:54:53
date last changed
2024-01-29 02:54:34
@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.}},
  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 (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Downregulation of miR-92a Is Associated with Aggressive Breast Cancer Features and Increased Tumour Macrophage Infiltration.}},
  url          = {{https://lup.lub.lu.se/search/files/4238453/3127281.pdf}},
  doi          = {{10.1371/journal.pone.0036051}},
  volume       = {{7}},
  year         = {{2012}},
}