title: Multitargeting activity of miR-24 inhibits long-term melatonin anticancer effects.
abstract: We have previously shown that melatonin exerts tumor suppressor activities by inducing the p38-p53 axis. This occurred within a few hours while no data are available on how melatonin pathway can be sustained on the long term. Here we show that miR-24, which has been demonstrated to target genes involved in the DNA repair process, targets p38, p53, PML and H2AX simultaneously. We show that long-term treatment with melatonin can decrease miR-24 levels post-transcriptionally, which pairs with a long-wave regulation of genes involved in cell proliferation, DNA damage, RNA metabolism and cell shape and transformation. Moreover, we show that melatonin can inhibit cell proliferation and migration, at least in part, by downregulating miR-24. Furthermore, we propose the involvement of hnRNP A1, which is downregulated by melatonin and involved in miRNA processing, in the regulation of miR-24 levels by melatonin. We conclude showing that miR-24 is upregulated in colon, breast and head and neck datasets and its levels negatively correlate with overall survival.
authors.affiliation: Molecular Chemoprevention Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Mori
authors.affiliation: Molecular Chemoprevention Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.|Translational Oncogenomics Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraiuolo
authors.affiliation: Molecular Chemoprevention Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Raffaela
authors.initials: R
authors.lastname: Santoro
authors.affiliation: Translational Oncogenomics Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sacconi
authors.affiliation: Translational Oncogenomics Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Frauke
authors.initials: F
authors.lastname: Goeman
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pallocca
authors.affiliation: Molecular Chemoprevention Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Pulito
authors.affiliation: Molecular Chemoprevention Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Etleva
authors.initials: E
authors.lastname: Korita
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fanciulli
authors.affiliation: Department of Oncology, Juravinski Cancer Center-McMaster University, Hamilton, ON L8V 5C2, Ontario, Canada.
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
authors.affiliation: Translational Oncogenomics Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.|Department of Oncology, Juravinski Cancer Center-McMaster University, Hamilton, ON L8V 5C2, Ontario, Canada.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Blandino
authors.affiliation: Molecular Chemoprevention Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.|Department of Oncology, Juravinski Cancer Center-McMaster University, Hamilton, ON L8V 5C2, Ontario, Canada.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Strano
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; C543845:MIRN24 microRNA, human; D035683:MicroRNAs; D008550:Melatonin
keywords: PML; RNA-Seq; melatonin; miR-24; p53