Downregulation of miR-92a Is Associated with Aggressive Breast Cancer Features and Increased Tumour Macrophage Infiltration.
(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:
https://lup.lub.lu.se/record/2609066
- author
- Björner, Sofie LU ; Möller, Christina LU ; Jirström, Karin LU ; Lee, Alexander ; Busch, Susann ; Lamb, Rebecca and Landberg, Göran LU
- organization
- publishing date
- 2012
- 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<0.001), and downregulation of miR-92a promoted cell migration (p<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}}, }