Oncogene, 2011-05, Vol.30 (21), p.2463-2474
2011
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- Autor(en) / Beteiligte
- Titel
- miR-495 is upregulated by E12 E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1
- Ist Teil von
- Oncogene, 2011-05, Vol.30 (21), p.2463-2474
- Ort / Verlag
- Basingstoke: Nature Publishing Group
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- MicroRNAs (miRNAs) are involved in tumorigenecity by regulating specific oncogenes and tumor suppressor genes, and their roles in breast cancer stem cells (BCSCs) are becoming apparent. Distinct from the CD44(+)/CD24(-/low) sub-population, we have isolated a novel PROCR(+)/ESA(+) BCSC sub-population. To explore miRNA-regulatory mechanisms in this sub-population, we performed miRNA expression profiling and found miR-495 as the most highly upegulated miRNA in PROCR(+)/ESA(+) cells. Coincidently, high upregulation of miR-495 was also found in CD44(+)/CD24(-/low) BCSCs, reflecting its potential importance in maintaining common BCSC properties. Ectopic expression of miR-495 in breast cancer cells promoted their colony formation in vitro and tumorigenesis in mice. miR-495 directly suppressed E-cadherin expression to promote cell invasion and inhibited REDD1 expression to enhance cell proliferation in hypoxia through post-transcriptional mechanism. miR-495 expression was directly modulated by transcription factor E12/E47, which itself is highly expressed in BCSCs. These findings reveal a novel regulatory pathway centered on miR-495 that contributes to BCSC properties and hypoxia resistance.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/onc.2010.618Titel-ID: cdi_proquest_miscellaneous_876229626
- Format
- –
- Schlagworte
- Animals, Base Sequence, Biological and medical sciences, Breast cancer, Breast Neoplasms - genetics, Breast Neoplasms - metabolism, Breast Neoplasms - pathology, Cadherins - genetics, Cadherins - metabolism, Care and treatment, CD44 antigen, Cell Hypoxia, Cell Line, Cell Line, Tumor, Cell physiology, Cell proliferation, Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes, Cellular biology, Development and progression, Down-Regulation, E-cadherin, Ectopic expression, Female, Fundamental and applied biological sciences. Psychology, Gene Expression Profiling, Genetic aspects, Genetic regulation, Gynecology. Andrology. Obstetrics, HEK293 Cells, Humans, Hypoxia, Immunoblotting, Mammary gland diseases, Mammary Neoplasms, Experimental - genetics, Mammary Neoplasms, Experimental - metabolism, Mammary Neoplasms, Experimental - pathology, Medical sciences, Mice, Mice, Inbred NOD, Mice, SCID, MicroRNA, MicroRNAs, MicroRNAs - genetics, miRNA, Molecular and cellular biology, Molecular Sequence Data, Neoplastic Stem Cells - metabolism, Oncology, Physiological aspects, Post-transcription, Promoter Regions, Genetic - genetics, Protein Binding, Reverse Transcriptase Polymerase Chain Reaction, Ribonucleic acid, RNA, Stem cell transplantation, Stem cells, Transcription Factor 3 - genetics, Transcription Factor 3 - metabolism, Transcription Factors - genetics, Transcription Factors - metabolism, Transplantation, Heterologous, Tumor suppressor genes, Tumorigenesis, Tumors