title: HER2-encoded mir-4728 forms a receptor-independent circuit with miR-21-5p through the non-canonical poly(A) polymerase PAPD5.
abstract: We previously reported that the human HER2 gene encodes the intronic microRNA mir-4728, which is overexpressed together with its oncogenic host gene and may act independently of the HER2 receptor. More recently, we also reported that the oncogenic miR-21-5p is regulated by 3' tailing and trimming by the non-canonical poly(A) polymerase PAPD5 and the ribonuclease PARN. Here we demonstrate a dual function for the HER2 locus in upregulation of miR-21-5p; while HER2 signalling activates transcription of mir-21, miR-4728-3p specifically stabilises miR-21-5p through inhibition of PAPD5. Our results establish a new and unexpected oncogenic role for the HER2 locus that is not currently being targeted by any anti-HER2 therapy.
authors.affiliation: Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund University Cancer Center, Lund, Sweden.|BioCARE, Strategic Cancer Research Program, Lund, Sweden.
authors.forename: Inga
authors.initials: I
authors.lastname: Newie
authors.affiliation: Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund University Cancer Center, Lund, Sweden.|BioCARE, Strategic Cancer Research Program, Lund, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Søkilde
authors.affiliation: Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund University Cancer Center, Lund, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Persson
authors.affiliation: Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund University Cancer Center, Lund, Sweden.
authors.forename: Thiago
authors.initials: T
authors.lastname: Jacomasso
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andrej
authors.initials: A
authors.lastname: Gorbatenko
authors.affiliation: Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund University Cancer Center, Lund, Sweden.|BioCARE, Strategic Cancer Research Program, Lund, Sweden.|CREATE Health, Strategic Centre for Translational Cancer Research, Lund, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Borg
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan.
authors.forename: Michiel
authors.initials: M
authors.lastname: de Hoon
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Stine F
authors.initials: SF
authors.lastname: Pedersen
authors.affiliation: Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund University Cancer Center, Lund, Sweden.|BioCARE, Strategic Cancer Research Program, Lund, Sweden.|CREATE Health, Strategic Centre for Translational Cancer Research, Lund, Sweden.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rovira
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012316:RNA Nucleotidyltransferases / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D012316:RNA Nucleotidyltransferases; D018719:Erb-b2 Receptor Tyrosine Kinases; C524940:MIRN21 microRNA, human; C000605129:MIRN4728 microRNA, human; C508053:ERBB2 protein, human; C567954:TENT4B protein, human