Characterization of GECPAR, a noncoding RNA that regulates the transcriptional program of diffuse large B-cell lymphoma
Sara Napoli,
Luciano Cascione,
Andrea Rinaldi,
Filippo Spriano,
Francesca Guidetti,
Fangwen Zhang,
Maria Teresa Cacciapuoti,
Afua Adjeiwaa Mensah,
Giulio Sartori,
Nicolas Munz,
Mattia Forcato,
Silvio Bicciato,
Annalisa Chiappella,
Paola Ghione,
Olivier Elemento,
Leandro Cerchietti,
Giorgio Inghirami,
Francesco Bertoni
Affiliations
Sara Napoli
Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona
Luciano Cascione
Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland; SIB Swiss Institute of Bioinformatics, Lausanne
Andrea Rinaldi
Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona
Filippo Spriano
Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona
Francesca Guidetti
Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona
Fangwen Zhang
Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona
Maria Teresa Cacciapuoti
Pathology and Laboratory Medicine Department, Weill Cornell Medicine, New York, NY
Afua Adjeiwaa Mensah
Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona
Giulio Sartori
Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona
Nicolas Munz
Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona
Mattia Forcato
Center for Genome Research, Department of Life Sciences University of Modena and Reggio
Silvio Bicciato
Center for Genome Research, Department of Life Sciences University of Modena and Reggio
Annalisa Chiappella
Ematologia, A.O.U. Città della Salute e della Scienza di Torino, Turin
Paola Ghione
Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, 10021
Olivier Elemento
Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY
Leandro Cerchietti
Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, 10021
Giorgio Inghirami
Pathology and Laboratory Medicine Department, Weill Cornell Medicine, New York, NY
Francesco Bertoni
Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland; Oncology Institute of Southern Switzerland, Bellinzona
Enhancers are regulatory regions of DNA, which play a key role in cell-type specific differentiation and development. Most active enhancers are transcribed into enhancer RNA (eRNA) that can regulate transcription of target genes by means of in cis as well as in trans action. eRNA stabilize contacts between distal genomic regions and mediate the interaction of DNA with master transcription factors. Here, we characterized an enhancer eRNA, GECPAR (germinal center proliferative adapter RNA), which is specifically transcribed in normal and neoplastic germinal center B cells from the super-enhancer of POU2AF1, a key regulatory gene of the germinal center reaction. Using diffuse large B-cell lymphoma cell line models, we demonstrated the tumor suppressor activity of GECPAR, which is mediated via its transcriptional regulation of proliferation and differentiation genes, particularly MYC and the Wnt pathway.
