title: Copy number gain of hsa-miR-569 at 3q26.2 leads to loss of TP53INP1 and aggressiveness of epithelial cancers.
abstract: Small noncoding miRNAs represent underexplored targets of genomic aberrations and emerging therapeutic targets. The 3q26.2 amplicon is among the most frequent genomic aberrations in multiple cancer lineages including ovarian and breast cancers. We demonstrate that hsa-miR-569 (hereafter designated as miR569), which is overexpressed in a subset of ovarian and breast cancers, at least in part due to the 3q26.2 amplicon, alters cell survival and proliferation. Downregulation of TP53INP1 expression by miR569 is required for the effects of miR569 on survival and proliferation. Targeting miR569 sensitizes ovarian and breast cancer cells overexpressing miR569 to cisplatin by increasing cell death both in vitro and in vivo. Thus targeting miR569 could potentially benefit patients with the 3q26.2 amplicon and subsequent miR569 elevation.
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. Electronic address: pcraghavan@mdanderson.org.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Chaluvally-Raghavan
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Sunila
authors.initials: S
authors.lastname: Pradeep
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Hamilton
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital, the Norwegian Radium Hospital, 0424 Oslo, Norway; The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0424 Oslo, Norway.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Rajesha
authors.initials: R
authors.lastname: Rupaimoole
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Moss
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Shuangxing
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Thoracic, Head and Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Chad V
authors.initials: CV
authors.lastname: Pecot
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital, the Norwegian Radium Hospital, 0424 Oslo, Norway; The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0424 Oslo, Norway.
authors.forename: Miriam R
authors.initials: MR
authors.lastname: Aure
authors.affiliation: INSERM U1068, CRCM, Cell Stress, Marseille F-13009, France; Institut Paoli-Calmettes, 13273 Marseille Cedex 9, France; UMR7258, CNRS, Aix-Marseille University, Marseille F-13009, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Peuget
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Rodriguez-Aguayo
authors.affiliation: Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Hee-Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Avinashnarayan
authors.initials: A
authors.lastname: Venkatanarayan
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital, the Norwegian Radium Hospital, 0424 Oslo, Norway; The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0424 Oslo, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Krohn
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital, the Norwegian Radium Hospital, 0424 Oslo, Norway; The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0424 Oslo, Norway.
authors.forename: Vessela N
authors.initials: VN
authors.lastname: Kristensen
authors.affiliation: Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gagea
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Prahlad
authors.initials: P
authors.lastname: Ram
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Lorenzi
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital, the Norwegian Radium Hospital, 0424 Oslo, Norway; The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0424 Oslo, Norway.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Koei
authors.initials: K
authors.lastname: Chin
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Gray
authors.affiliation: INSERM U1068, CRCM, Cell Stress, Marseille F-13009, France; Institut Paoli-Calmettes, 13273 Marseille Cedex 9, France; UMR7258, CNRS, Aix-Marseille University, Marseille F-13009, France.
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Dusetti
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Sean E
authors.initials: SE
authors.lastname: McGuire
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Elsa R
authors.initials: ER
authors.lastname: Flores
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. Electronic address: gmills@mdanderson.org.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002893:Chromosomes, Human, Pair 3; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D005784:Gene Amplification; D020440:Gene Duplication; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009374:Neoplasms, Experimental; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D006360:Heat-Shock Proteins; C000595199:MIRN-569 microRNA, human; C000595200:MIRN-569 microRNA, mouse; D035683:MicroRNAs; D009687:Nuclear Proteins; C429767:TP53INP1 protein, human; C518507:tumor protein 53-induced nuclear protein 1, mouse; D002945:Cisplatin