title: miR-155 is positively regulated by CBX7 in mouse embryonic fibroblasts and colon carcinomas, and targets the KRAS oncogene.
abstract: Loss of CBX7 expression has been described in several malignant neoplasias, including human colon and thyroid carcinomas proposing CBX7 as a tumor suppressor gene with a key role in cancer progression. This role is supported from the development of benign and malignant neoplasias in Cbx7 null mice. The aim of our work has been to investigate the mechanisms underlying the CBX7 oncosuppressor activity by analyzing the microRNAs (miRNAs) regulated by CBX7.
  
  
  
  The miRNA expression profiles of the mouse embryonic fibroblasts (MEFs) null for Cbx7 and the wild-type counterpart were analyzed by the miRNACHIP microarray and then validated by qRT-PCR. To asses KRAS as target of miR-155 we evaluated the protein levels after transfection of the synthetic miR-155. Human colon carcinoma samples have been investigated for the expression of CBX7 and miR-155.
  
  
  
  Twenty miRNAs were found upregulated and nine, including miR-155, downregulated in cbx7-null MEFS in comparison with the wild-type ones. Then, we focused on miR-155 since several studies have shown its deregulated expression in several human malignancies and, moreover, was the most downregulated miRNA. Subsequently, we searched for miR-155 target genes demonstrating that KRAS protein levels are directly modulated by miR-155. A direct significant correlation (r = 0.6779) between CBX7 and miR-155 expression levels was found in a set of human colon carcinoma tissue samples.
  
  
  
  miR-155 is positively regulated by CBX7 in MEFs and colon carcinomas, and has KRAS as one of the target genes likely accounting for the anti-apoptotic activity ascribed to miR-155 in some tissue contexts.
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Forzati
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: De Martino
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Esposito
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Sepe
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Pellecchia
authors.affiliation: Dipartimento di Sanità Pubblica, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Malapelle
authors.affiliation: Unità di Chirurgia Colorettale, Dipartimento di Scienze Mediche, Chirurgiche, Neurologiche e dell'Invecchiamento, Seconda Università di Napoli, Naples, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Pellino
authors.affiliation: Istituto Nazionale dei Tumori, Fondazione Pascale, Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Naples, Italy. alfusco@unina.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D011905:Genes, ras; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C503627:CBX7 protein, human; C519505:Cbx7 protein, mouse; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D063150:Polycomb Repressive Complex 1
keywords: CBX7; Colon carcinoma; KRAS; miR-155