PMID- 24863696 OWN - NLM STAT- MEDLINE DCOM- 20150818 LR - 20220321 IS - 1573-7217 (Electronic) IS - 0167-6806 (Print) IS - 0167-6806 (Linking) VI - 146 IP - 1 DP - 2014 Jul TI - The metastatic potential of triple-negative breast cancer is decreased via caloric restriction-mediated reduction of the miR-17~92 cluster. PG - 41-50 LID - 10.1007/s10549-014-2978-7 [doi] AB - Caloric restriction (CR) has been shown to cause tumor regression in models of triple-negative breast cancer (TNBC), and the regression is augmented when coupled with ionizing radiation (IR). In this study, we sought to determine if the molecular interaction between CR and IR could be mediated by microRNA (miR). miR arrays revealed 3 miRs in the miR-17~92 cluster as most significantly down regulated when CR is combined with IR. In vivo, CR and IR down regulated miR-17/20 in 2 TNBC models. To elucidate the mechanism by which this cluster regulates the response to CR, cDNA arrays were performed and the top 5 statistically significant gene ontology terms with high fold changes were all associated with extracellular matrix (ECM) and metastases. In silico analysis revealed 4 potential targets of the miR-17~92 cluster related to ECM: collagen 4 alpha 3, laminin alpha 3, and metallopeptidase inhibitors 2 and 3, which were confirmed by luciferase assays. The overexpression or silencing of miR-17/20a demonstrated that those miRs directly affected the ECM proteins. Furthermore, we found that CR-mediated inhibition of miR-17/20a can regulate the expression of ECM proteins. Functionally, we demonstrate that CR decreases the metastatic potential of cells which further demonstrates the importance of the ECM. In conclusion, CR can be used as a potential treatment for cancer because it may alter many molecular targets concurrently and decrease metastatic potential for TNBC. FAU - Jin, Lianjin AU - Jin L AD - Department of Radiation Oncology, Thomas Jefferson University, Phiadelphia, PA, 19107, USA. FAU - Lim, Meng AU - Lim M FAU - Zhao, Shuping AU - Zhao S FAU - Sano, Yuri AU - Sano Y FAU - Simone, Brittany A AU - Simone BA FAU - Savage, Jason E AU - Savage JE FAU - Wickstrom, Eric AU - Wickstrom E FAU - Camphausen, Kevin AU - Camphausen K FAU - Pestell, Richard G AU - Pestell RG FAU - Simone, Nicole L AU - Simone NL LA - eng GR - P30 CA056036/CA/NCI NIH HHS/United States GR - ZIA BC010873-03/Intramural NIH HHS/United States GR - P30-CA56036/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140527 PL - Netherlands TA - Breast Cancer Res Treat JT - Breast cancer research and treatment JID - 8111104 RN - 0 (Extracellular Matrix Proteins) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 0 (Tissue Inhibitor of Metalloproteinase-3) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) SB - IM MH - Animals MH - Base Sequence MH - Binding Sites MH - Caloric Restriction MH - Cell Line, Tumor MH - Cell Movement MH - Disease Models, Animal MH - Extracellular Matrix Proteins/chemistry/genetics/metabolism MH - Female MH - Gene Expression MH - Humans MH - Mice MH - MicroRNAs/chemistry/*genetics MH - *Multigene Family MH - Neoplasm Metastasis MH - RNA, Messenger/chemistry/genetics MH - Radiation, Ionizing MH - Sequence Alignment MH - Tissue Inhibitor of Metalloproteinase-2/genetics/metabolism MH - Tissue Inhibitor of Metalloproteinase-3/genetics/metabolism MH - Triple Negative Breast Neoplasms/*genetics/metabolism/*pathology PMC - PMC4157915 MID - NIHMS613371 COIS- Conflict of interest The authors declare that they have no conflict of interest. EDAT- 2014/05/28 06:00 MHDA- 2015/08/19 06:00 PMCR- 2015/07/01 CRDT- 2014/05/28 06:00 PHST- 2014/02/01 00:00 [received] PHST- 2014/04/19 00:00 [accepted] PHST- 2014/05/28 06:00 [entrez] PHST- 2014/05/28 06:00 [pubmed] PHST- 2015/08/19 06:00 [medline] PHST- 2015/07/01 00:00 [pmc-release] AID - 10.1007/s10549-014-2978-7 [doi] PST - ppublish SO - Breast Cancer Res Treat. 2014 Jul;146(1):41-50. doi: 10.1007/s10549-014-2978-7. Epub 2014 May 27.