title: HMGA1 pseudogenes as candidate proto-oncogenic competitive endogenous RNAs.
abstract: The High Mobility Group A (HMGA) are nuclear proteins that participate in the organization of nucleoprotein complexes involved in chromatin structure, replication and gene transcription. HMGA overexpression is a feature of human cancer and plays a causal role in cell transformation. Since non-coding RNAs and pseudogenes are now recognized to be important in physiology and disease, we investigated HMGA1 pseudogenes in cancer settings using bioinformatics analysis. Here we report the identification and characterization of two HMGA1 non-coding pseudogenes, HMGA1P6 and HMGA1P7. We show that their overexpression increases the levels of HMGA1 and other cancer-related proteins by inhibiting the suppression of their synthesis mediated by microRNAs. Consistently, embryonic fibroblasts from HMGA1P7-overexpressing transgenic mice displayed a higher growth rate and reduced susceptibility to senescence. Moreover, HMGA1P6 and HMGA1P7 were overexpressed in human anaplastic thyroid carcinomas, which are highly aggressive, but not in differentiated papillary carcinomas, which are less aggressive. Lastly, the expression of the HMGA1 pseudogenes was significantly correlated with HMGA1 protein levels thereby implicating HMGA1P overexpression in cancer progression. In conclusion, HMGA1P6 and HMGA1P7 are potential proto-oncogenic competitive endogenous RNAs.
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, 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 del CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, 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 del CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Petti
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, 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 del CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Tornincasa
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Federico
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 del CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Giovanna Maria
authors.initials: GM
authors.lastname: Pierantoni
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D016922:Cellular Senescence; D019295:Computational Biology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D024003:HMGA Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011544:Pseudogenes / Q000235:genetics*; D034622:RNA Interference; D065646:Thyroid Carcinoma, Anaplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014162:Transfection
chemical_list: D024003:HMGA Proteins; D035683:MicroRNAs