Intracellular and extracellular microRNAs in breast cancer.
BACKGROUND
Successful treatment of breast cancer is enhanced by early detection and, if possible, subsequent patient-tailored therapy. Toward this goal, it is essential to identify and understand the most relevant panels of biomarkers, some of which may also have relevance as therapeutic targets.


METHODS
We critically reviewed published literature on microRNAs (miRNAs) as relevant to breast cancer.


CONCLUSIONS
Since the initial recognition of the association of miRNAs with breast cancer in 2005, studies involving cell lines, in vivo models, and clinical specimens have implicated several functions for miRNAs, including suppressing oncogenesis and tumors, promoting or inhibiting metastasis, and increasing sensitivity or resistance to chemotherapy and targeted agents in breast cancer. For example, miR-21 is overexpressed in both male and female breast tumors compared with normal breast tissue and has been associated with advanced stage, lymph node positivity, and reduced survival time. miR-21 knock-down in cell-line models has been associated with increased sensitivity to topotecan and taxol in vitro and the limitation of lung metastasis in vivo. Furthermore, the discovery of extracellular miRNAs (including miR-21), existing either freely or in exosomes in the systemic circulation, has led to the possibility that such molecules may serve as biomarkers for ongoing patient monitoring. Although additional investigations are necessary to fully exploit the use of miRNAs in breast cancer, there is increasing evidence that miRNAs have potential not only to facilitate the determination of diagnosis and prognosis and the prediction of response to treatment, but also to act as therapeutic targets and replacement therapies.
School of Pharmacy and Pharmaceutical Sciences and Molecular Therapeutics for Cancer Ireland (MTCI), Trinity College Dublin, Dublin, Ireland.
Claire
C
Corcoran
Anne M
AM
Friel
Michael J
MJ
Duffy
John
J
Crown
Lorraine
L
O'Driscoll
D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009857:Oncogenes; D011379:Prognosis
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D035683:MicroRNAs