Hwang-Verslues W.W.Chang P.-H.Wei P.-C.Yang C.-Y.Huang C.-K.WEN-HUNG KUOShew J.-Y.KING-JEN CHANGLee E.Y.-H.P.Lee W.-H.2020-03-242020-03-2420110950-9232https://www.scopus.com/inward/record.uri?eid=2-s2.0-79957613439&doi=10.1038%2fonc.2010.618&partnerID=40&md5=1519eb5236706ba03b7922de4afc0ec4https://scholars.lib.ntu.edu.tw/handle/123456789/478421MicroRNAs (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.breast cancer stem cell; E-cadherin; E12/E47; hypoxia resistance; miR-495; REDD1[SDGs]SDG3CD24 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; Musjournal article10.1038/onc.2010.618212584092-s2.0-79957613439