title: IFN-β antiproliferative effect and miRNA regulation in Human Papilloma Virus E6- and E7-transformed keratinocytes.
abstract: Human Papilloma Viruses (HPVs) are the causative agents of cervical cancer although other types of cancers are associated with HPV infection. Type I Interferons can interfere with HPV E6- and/or E7-dependent transformation and can affect microRNA (miRNA) expression. Cancer cells show a specific pattern of miRNA expression and HPVs are able to modulate miRNAs expressed in infected cells. Keratinocytes transduced with E6 and E7 from mucosal HPV-16 or cutaneous HPV-38 (K16 and K38) were studied to analyze the involvement of HPV oncoproteins in the anti-proliferative activity of IFN-β. In view of our previous data showing senescence induction by the cytokine in K38 cells, we observe that IFN-β treatment leads to p53-indipendent apoptosis in K16 cells whereas induces senescence in K16 cells if E6 is silenced and p53 expression is restored. The levels of selected miRNAs, deregulated in K16 and K38 cells, can be modulated by IFN-β when E6 and E7 proteins of HPV-16, but not HPV-38, are expressed.
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Maria Vincenza
authors.initials: MV
authors.lastname: Chiantore
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Mangino
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Iuliano
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy.
authors.forename: Maria Simona
authors.initials: MS
authors.lastname: Zangrillo
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: De Lillis
authors.affiliation: Department of Veterinary Public Health & Food Safety, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Vaccari
authors.affiliation: Infections and Cancer Biology Group, International Agency for Research on Cancer, 69372 Lyon, France.
authors.forename: Rosita
authors.initials: R
authors.lastname: Accardi
authors.affiliation: Infections and Cancer Biology Group, International Agency for Research on Cancer, 69372 Lyon, France.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy; Institute of Molecular Biology and Pathology, Consiglio Nazionale delle Ricerche, 00161 Rome, Italy.
authors.forename: Gianna
authors.initials: G
authors.lastname: Fiorucci
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy; Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy; Institute of Molecular Biology and Pathology, Consiglio Nazionale delle Ricerche, 00161 Rome, Italy. Electronic address: giovanna.romeo@uniroma1.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Romeo
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002461:Cell Line, Transformed; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D035683:MicroRNAs; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C059731:oncogene protein E7, Human papillomavirus type 16; D016899:Interferon-beta
keywords: Apoptosis; Human Papilloma Virus; Interferon; MicroRNAs; Senescence