Tavazoie, S. F. et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451, 147-152

Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nature (Impact Factor: 41.46). 02/2008; 451(7175):147-52. DOI: 10.1038/nature06487
Source: PubMed


A search for general regulators of cancer metastasis has yielded a set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential. Here we show that restoring the expression of these microRNAs in malignant cells suppresses lung and bone metastasis by human cancer cells in vivo. Of these microRNAs, miR-126 restoration reduces overall tumour growth and proliferation, whereas miR-335 inhibits metastatic cell invasion. miR-335 regulates a set of genes whose collective expression in a large cohort of human tumours is associated with risk of distal metastasis. miR-335 suppresses metastasis and migration through targeting of the progenitor cell transcription factor SOX4 and extracellular matrix component tenascin C. Expression of miR-126 and miR-335 is lost in the majority of primary breast tumours from patients who relapse, and the loss of expression of either microRNA is associated with poor distal metastasis-free survival. miR-335 and miR-126 are thus identified as metastasis suppressor microRNAs in human breast cancer.

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Available from: Thordur Oskarsson, Mar 14, 2014
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    • "MicroRNAs is a novel and vital class of tumour and oncogene suppressing genes (Tazawa et al., 2007). MicroRNAs involvement in tumours are centred on distinctive expression in neoplastic tissue in a tumorous specific manner as compare to normal tissue (Tavazoie et al., 2008) and in primary tumours when compare to metastatic tissues (Volinia et al., 2006). MiRNAs are supposed to work as oncogenes, when there expression is elevated in tumours. "
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    ABSTRACT: MicroRNAs (miRNA) - a novel class of small noncoding RNAs genes. Their final product is a twenty two nucleotides functional molecule of RNA. These small non-coding RNAs silence and target several genes through varied signalling pathways that include important physiological networks. MiRNAs regulates post-transcriptional expression of genes. The miRNA was discovered as small temporal RNA (stRNA) regulating development transition in Caenorhabditis elegans. The miRNAs have an enthusiastic part in neoplastic transformations either by elevating expression of oncogenes or reducing tumours suppressor genes and oncogene. Although miRNAs are key gene regulators, yet experimental and computational approaches are still scanty. Complete understanding of this prime regulating transcript class is still in need of exuberated research. The current article is reviewing miRNA, its discovery, role of miRNAs in suppression of tumours and oncogenes and role of miRNA in diagnosing cancer and its therapy.
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    • "Let-7 family (let-7-a1, a2, a3, b, c, d, e, f1, f2, g, i and miR-98) MYC, LIN28, HMGA2, caspase-3, H-RAS, PEBP1, ER-alpha MDA-MB-231, MCF-7, SKBR3, BT-IC Metastasis, modulating drug-induced cell death, apoptosis, differentiation, tumorigenicity, proliferation, differentiation [72] [73] [74] [75] [76] miR-335 SOX4, PTPRN2, TNC, MERTK MDA-MB-231 Metastasis [77] "
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    ABSTRACT: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide. MicroRNAs (miRNAs) are naturally-occurring, non-coding small RNA molecules that can modulate protein coding-genes, which makes it contributing to nearly all the physiological and pathological processes. Progression of breast cancer and resistance to endocrine therapies has been attributed to the possibility of hormone-responsive miRNAs involved in the regulation of certain signaling pathways. Methodology This review introduces better understanding of miRNAs to provide promising advances for treatment. miRNAs have multiple targets, and they were found to regulate different signaling pathways; consequently it is important to characterize their mechanisms of action and their cellular targets in order to introduce miRNAs as novel and promising therapies. This review summarizes the molecular mechanisms of miRNAs in TGF-Beta signaling, apoptosis, metastasis, cell cycle, ER-signaling, and drug resistance. Finally, miRNAs will be introduced as promising molecules to be used in the fight against breast cancer and its developed drug resistance. Copyright © 2014. Published by Elsevier Inc.
    Clinical Biochemistry 12/2014; 48(6). DOI:10.1016/j.clinbiochem.2014.12.013 · 2.28 Impact Factor
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    • "For example, microRNAs (miRNAs), as regulators of protein-coding genes, are attractive candidates as upstream regulators of metastatic progression because miRNAs can post-transcriptionally regulate entire sets of genes. Recent work has shown the use of miRNAs as metastasis suppressors [45]. Via our 3-D biomimetic bone model, we can easily analyze the migratory, proliferative and osteolytic capacities of genetically altered BrCa cells by manipulating miRNA expression (similar to the miRNA-transfected BrCa cells in our study). "
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    ABSTRACT: Traditional breast cancer (BrCa) bone metastasis models contain many limitations with regards to controllability, reproducibility, and flexibility of design. In this study, a novel biomimetic bone microenvironment was created by integrating hydroxyapatite (HA) and native bioactive factors deposited by osteogenic induction of human bone marrow mesenchymal stem cells (MSCs) within a cytocompatible chitosan hydrogel. It was found that a 10% nanocrystalline HA (nHA) chitosan scaffold exhibited the highest BrCa adhesion and proliferation when compared to chitosan scaffolds with 20% nHA, 10% and 20% microcrystalline HA as well as amorphous HA. This 3D tunable bone scaffold can provide a biologically relevant environment, increase cell-cell and cell-matrix interactions as found in native bone, and retain the behavior of BrCa cells with different metastasis potential (i.e., highly metastatic MDA-MB-231, less metastatic MCF-7 and transfected MDA-MB-231). The co-culture of MSCs and MDA-MB-231 in this bone model illustrated that MSCs have the capacity to upregulate the expression of the well-known metastasis-associated gene metadherin within BrCa cells. In summary, this study illustrates the capacity of our 3D bone model in creating a biomimetic environment conducive to recapitulating the behavior of metastatic BrCa cells, making it a promising tool for in vitro BrCa cell bone metastasis study and potential therapeutics discovery. Copyright © 2014. Published by Elsevier Ltd.
    Acta Biomaterialia 12/2014; 14. DOI:10.1016/j.actbio.2014.12.008 · 6.03 Impact Factor
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