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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    • "In the last decade, microRNAs have been frequently found deregulated in different human cancers, acting both as oncogenes or tumor suppressors. miRNAs are involved in basic cellular functions, including proliferation, cell death, differentiation, metabolism and, importantly, tumorigenesis789101113]. In addition, these noncoding RNAs have the capacity to target tens to hundreds of genes simultaneously[6]. "
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    • "Given the importance of PI(4,5)P 2 in multiple cellular processes, we were intrigued by the finding that transcriptomic profiling of MDA- MB-231 breast cancer cells and their in vivo-selected highly metastatic derivative LM2 subline revealed two genes, PTPRN2 and PLCB1, that possess known enzymatic activity for PI(4,5)P 2 to be both upregulated at the transcript and protein levels in LM2 cells (Figs 1A and B, and EV1A and B) (Minn et al, 2005; Tavazoie et al, 2008). We validated the upregulation of these genes in a second independent breast cancer cell line, CN34, and found that both genes exhibited markedly increased expression at the transcript and protein levels in the metastatic CNLM1a derivative subline relative to its parental cell population (Figs 1A and B, and EV1A and B). "
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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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