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
| Autor: | Po-Hao Chang, Yang Cy, Chun-Kai Huang, Pei-Chi Wei, Wendy W. Hwang-Verslues, Wen-Hung Kuo, Wen-Hwa Lee, Ey-Hp Lee, King-Jen Chang, Jin-Yuh Shew |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
medicine.medical_specialty Immunoblotting Molecular Sequence Data Transplantation Heterologous Down-Regulation Breast Neoplasms Mice SCID medicine.disease_cause Cell Line Mice Transcription Factor 3 Downregulation and upregulation Mice Inbred NOD Cell Line Tumor Internal medicine microRNA Genetics medicine Animals Humans Gene silencing Promoter Regions Genetic Molecular Biology Base Sequence biology Reverse Transcriptase Polymerase Chain Reaction Cadherin Gene Expression Profiling CD44 Mammary Neoplasms Experimental Cadherins Cell Hypoxia MicroRNAs HEK293 Cells Endocrinology Neoplastic Stem Cells biology.protein Cancer research Female Ectopic expression Stem cell Carcinogenesis Protein Binding Transcription Factors |
| Zdroj: | Oncogene. 30:2463-2474 |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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