title: miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma.
abstract: Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displays characteristic alterations in microRNA expression. Recently it was reported that the expression of a subset of microRNAs can distinguish between MPM and adenocarcinoma of the lung. However, the functional importance of these changes has yet to be investigated. We compared expression of miR-192, miR-193a-3p and the miR-200 family in normal pleura and MPM tumor specimens and found a statistically significant reduction in the levels of miR-193a-3p (3.1-fold) and miR-192 (2.8-fold) in MPM. Transfection of MPM cells with a miR-193a-3p mimic resulted in inhibition of growth and an induction of apoptosis and necrosis in vitro. The growth inhibitory effects of miR-193a-3p were associated with a decrease in MCL1 expression and were recapitulated by RNAi-mediated MCL1 silencing. Targeted delivery of miR-193a-3p mimic using EDV minicells inhibited MPM xenograft tumour growth, and was associated with increased apoptosis. In conclusion, miR-193a-3p appears to have importance in the biology of MPM and may represent a target for therapeutic intervention.
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, Australia.
authors.forename: Marissa
authors.initials: M
authors.lastname: Williams
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, Australia.|Sydney Medical School, The University of Sydney, Sydney, Australia.|Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Michaela B
authors.initials: MB
authors.lastname: Kirschner
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, Australia.
authors.forename: Yuen Yee
authors.initials: YY
authors.lastname: Cheng
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, Australia.|Faculty of Pharmacy, The University of Sydney, Sydney, Australia.
authors.forename: Jacky
authors.initials: J
authors.lastname: Hanh
authors.affiliation: EnGeneIC Ltd., Lane Cove, Australia.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Weiss
authors.affiliation: EnGeneIC Ltd., Lane Cove, Australia.
authors.forename: Nancy
authors.initials: N
authors.lastname: Mugridge
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, Australia.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Wright
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, Australia.|Sydney Medical School, The University of Sydney, Sydney, Australia.|Department of Medical Oncology, Concord Repatriation General Hospital, Sydney, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Linton
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, Australia.|Sydney Medical School, The University of Sydney, Sydney, Australia.|Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, Australia.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Kao
authors.affiliation: Cardiothoracic Surgical Unit, Royal Prince Alfred Hospital, The Baird Institute and Faculty of Medicine, The University of Sydney, Sydney, Australia.
authors.forename: J James B
authors.initials: JJ
authors.lastname: Edelman
authors.affiliation: Cardiothoracic Surgical Unit, Royal Prince Alfred Hospital, The Baird Institute and Faculty of Medicine, The University of Sydney, Sydney, Australia.|Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Vallely
authors.affiliation: Sydney Cardiothoracic Surgeons, RPA Medical Centre, Sydney, Australia.
authors.forename: Brian C
authors.initials: BC
authors.lastname: McCaughan
authors.affiliation: Sydney Medical School, The University of Sydney, Sydney, Australia.|Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Wendy
authors.initials: W
authors.lastname: Cooper
authors.affiliation: Department of Anatomical Pathology, Flinders Medical Centre, Adelaide, Australia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Klebe
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, Australia.|School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Ruby C Y
authors.initials: RC
authors.lastname: Lin
authors.affiliation: EnGeneIC Ltd., Lane Cove, Australia.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Brahmbhatt
authors.affiliation: EnGeneIC Ltd., Lane Cove, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: MacDiarmid
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, Australia.|Sydney Medical School, The University of Sydney, Sydney, Australia.
authors.forename: Nico
authors.initials: N
authors.lastname: van Zandwijk
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, Australia.|Sydney Medical School, The University of Sydney, Sydney, Australia.
authors.forename: Glen
authors.initials: G
authors.lastname: Reid
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism*; D000086002:Mesothelioma, Malignant; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics*; D009336:Necrosis; D009368:Neoplasm Transplantation; D010997:Pleural Neoplasms / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D034622:RNA Interference; D014162:Transfection
chemical_list: C579095:MCL1 protein, human; C546783:MIRN192 microRNA, human; C546818:MIRN193 microRNA, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein
keywords: mesothelioma; miR-193a; microRNA; tumor suppressor