Downregulation of tumor suppressive microRNAs in vivo in dense breast tissue of postmenopausal women
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Annelie Abrahamsson1, Alessandra Capodanno1, Anna Rzepecka2 and Charlotta Dabrosin1
1Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
2Department of Radiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
Charlotta Dabrosin, email: [email protected]
Keywords: mammary gland, microdialysis, mammography, extracellular miRNA, inflammation
Received: June 16, 2017 Accepted: August 19, 2017 Published: September 15, 2017
Women with dense breast tissue on mammography are at higher risk of developing breast cancer but the underlying mechanisms are not well understood. De-regulation of microRNAs (miRNAs) has been associated with the onset of breast cancer. miRNAs in the extracellular space participate in the regulation of the local tissue microenvironment.
Here, we recruited 39 healthy postmenopausal women attending their mammography-screen that were assessed having extreme dense or entirely fatty breasts (nondense). Microdialysis was performed in breast tissue and a reference catheter was inserted in abdominal subcutaneous fat for local sampling of extracellular compounds. Three miRNAs, associated with tumor suppression, miR-193b, miR-365a, and miR-452 were significantly down-regulated in dense breast tissue compared with nondense breast tissue. In addition, miR-452 exhibited significant negative correlations with several pro-inflammatory cytokines in vivo, which was confirmed in vitro by overexpression of miR-452 in breast cancer cells. No differences were found of miR-21, -29a, -30c, 146a, -148a, -203, or -451 in breast tissue and no miRs were different in plasma. Extracellular miRNAs may be among factors that should be included in studies of novel prevention strategies for breast cancer.
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