title: Epigenetic silencing of miR-145-5p contributes to brain metastasis.
abstract: Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145's promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis.
authors.affiliation: Translational Oncogenomics Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Donzelli
authors.affiliation: Molecular Chemoprevention Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Mori
authors.affiliation: Translational Oncogenomics Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Bellissimo
authors.affiliation: Translational Oncogenomics Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sacconi
authors.affiliation: Department of Pathology, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Casini
authors.affiliation: Translational Oncogenomics Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Frixa
authors.affiliation: Takis S.r.l., Roma, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Roscilli
authors.affiliation: Takis S.r.l., Roma, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurisicchio
authors.affiliation: Unit of Thoracic Surgery, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Facciolo
authors.affiliation: Department of Neurosurgery, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pompili
authors.affiliation: Department of Pathology, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Carosi
authors.affiliation: Department of Pathology, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Pescarmona
authors.affiliation: Laboratory of Cell Signaling, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Oreste
authors.initials: O
authors.lastname: Segatto
authors.affiliation: Department of Oncology, Faculty of Health Science, McMaster University, Hamilton, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Pond
authors.affiliation: Department of Oncology, Faculty of Health Science, McMaster University, Hamilton, Canada.
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
authors.affiliation: Department of Neurosurgery, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Telera
authors.affiliation: Molecular Chemoprevention Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.|Department of Oncology, Faculty of Health Science, McMaster University, Hamilton, Canada.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Strano
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yosef
authors.initials: Y
authors.lastname: Yarden
authors.affiliation: Translational Oncogenomics Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.|Department of Oncology, Faculty of Health Science, McMaster University, Hamilton, Canada.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Blandino
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018899:CpG Islands; D019175:DNA Methylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D015398:Signal Transduction
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs
keywords: brain metastases; epigenetic modifications; lung cancer; migration; mir-145-5p