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
Journal
Oncogene
Journal Volume
30
Journal Issue
21
Pages
2463-2474
Date Issued
2011
Author(s)
Hwang-Verslues W.W.
Chang P.-H.
Wei P.-C.
Yang C.-Y.
Huang C.-K.
Shew J.-Y.
Lee E.Y.-H.P.
Lee W.-H.
Abstract
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. ? 2011 Macmillan Publishers Limited All rights reserved.
Subjects
breast cancer stem cell; E-cadherin; E12/E47; hypoxia resistance; miR-495; REDD1
SDGs
Other Subjects
CD24 antigen; Hermes antigen; microRNA; microRNA 125b; microRNA 127; microRNA 142 3; microRNA 155; microRNA 195; microRNA 199a; microRNA 199b; microRNA 203; microRNA 214; microRNA 376a; microRNA 409 3p; microRNA 485 3p; microRNA 495; microRNA 517b; microRNA 523; microRNA 544; microRNA 671 3p; protein REDD1; regulator protein; transcription factor; transcription factor e12; transcription factor e47; unclassified drug; uvomorulin; animal cell; article; breast cancer; breast carcinogenesis; cancer resistance; cancer stem cell; cell hypoxia; cell invasion; cell proliferation; colony formation; controlled study; down regulation; gene expression profiling; gene expression regulation; in vitro study; mouse; nonhuman; priority journal; protein expression; upregulation; Animals; Base Sequence; Breast Neoplasms; Cadherins; Cell Hypoxia; Cell Line; Cell Line, Tumor; Down-Regulation; Female; Gene Expression Profiling; HEK293 Cells; Humans; Immunoblotting; Mammary Neoplasms, Experimental; Mice; Mice, Inbred NOD; Mice, SCID; MicroRNAs; Molecular Sequence Data; Neoplastic Stem Cells; Promoter Regions, Genetic; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factor 3; Transcription Factors; Transplantation, Heterologous; Mus
Type
journal article