title: The long intergenic non-coding RNA CCR492 functions as a let-7 competitive endogenous RNA to regulate c-Myc expression.
abstract: In mammals the cell-cycle progression through the G1 phase is a tightly regulated process mediated by the transcriptional activation of early genes in response to mitogenic stimuli, whose dysregulation often leads to tumorigenesis. We here report the discovery by RNA-seq of cell-cycle regulated (CCR) long intergenic non-coding RNAs (lincRNAs), potentially involved in the control of the cell-cycle progression. We identified 10 novel lincRNAs expressed in response to serum treatment in mouse embryonic fibroblasts (MEFs) and in BALB/c fibroblasts, comparably to early genes. By loss-of-function experiments we found that lincRNA CCR492 is required for G1/S progression, localizes in the cell cytoplasm and contains 4 let-7 microRNA recognition elements (MREs). Mechanistically, CCR492 functions as a competing endogenous RNA (ceRNA) to antagonize the function of let-7 microRNAs, leading to the de-repression of c-Myc. Moreover, we show that ectopic expression of CCR492 along with a constitutively active H-Ras promotes cell transformation. Thus, we identified a new lincRNA expressed as an early gene in mammalian cells to regulate the cell-cycle progression by upregulating c-Myc expression.
authors.affiliation: Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università di Torino, Via Accademia Albertina 13, 10123 Torino, Italy; Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Torino, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Maldotti
authors.affiliation: Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università di Torino, Via Accademia Albertina 13, 10123 Torino, Italy; Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Torino, Italy.
authors.forename: Danny
authors.initials: D
authors.lastname: Incarnato
authors.affiliation: Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Torino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Neri
authors.affiliation: Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università di Torino, Via Accademia Albertina 13, 10123 Torino, Italy; Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Torino, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Krepelova
authors.affiliation: Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Torino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Rapelli
authors.affiliation: Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università di Torino, Via Accademia Albertina 13, 10123 Torino, Italy; Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Torino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Anselmi
authors.affiliation: Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Torino, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Parlato
authors.affiliation: Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università di Torino, Via Accademia Albertina 13, 10123 Torino, Italy; Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Torino, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Basile
authors.affiliation: Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Università di Torino, Via Nizza 52, Torino, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Dettori
authors.affiliation: Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Università di Torino, Via Nizza 52, Torino, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Calogero
authors.affiliation: Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università di Torino, Via Accademia Albertina 13, 10123 Torino, Italy; Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Torino, Italy. Electronic address: salvatore.oliviero@unito.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Oliviero
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D016193:G1 Phase; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D035683:MicroRNAs; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; C542687:mirnlet7 microRNA, mouse; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Cell cycle; Let-7; Non-coding RNA; c-Myc; ceRNA