title: miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion.
abstract: Whether epithelial-mesenchymal transition (EMT) is always linked to increased tumorigenicity is controversial. Through microRNA (miRNA) expression profiling of mammary epithelial cells overexpressing Twist, Snail or ZEB1, we identified miR-100 as a novel EMT inducer. Surprisingly, miR-100 inhibits the tumorigenicity, motility and invasiveness of mammary tumor cells, and is commonly downregulated in human breast cancer due to hypermethylation of its host gene MIR100HG. The EMT-inducing and tumor-suppressing effects of miR-100 are mediated by distinct targets. While miR-100 downregulates E-cadherin by targeting SMARCA5, a regulator of CDH1 promoter methylation, this miRNA suppresses tumorigenesis, cell movement and invasion in vitro and in vivo through direct targeting of HOXA1, a gene that is both oncogenic and pro-invasive, leading to repression of multiple HOXA1 downstream targets involved in oncogenesis and invasiveness. These findings provide a proof-of-principle that EMT and tumorigenicity are not always associated and that certain EMT inducers can inhibit tumorigenesis, migration and invasion.
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Dahu
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America ; Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Peijing
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America ; Cancer Biology Program, Graduate School of Biomedical Sciences, The University of Texas Health, Science Center at Houston, Houston, Texas, United States of America.
authors.forename: M James
authors.initials: MJ
authors.lastname: You
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.
authors.forename: Sumeet
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America ; Cancer Biology Program, Graduate School of Biomedical Sciences, The University of Texas Health, Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Han
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America ; Cancer Biology Program, Graduate School of Biomedical Sciences, The University of Texas Health, Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D064200:Cdh1 Proteins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis; D000099261:Homeobox A1 Protein
chemical_list: D015820:Cadherins; D064200:Cdh1 Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D014157:Transcription Factors; D000099261:Homeobox A1 Protein; C577584:FZR1 protein, human; C544266:MIRN100 microRNA, human