C/EBPα-p30 protein induces expression of the oncogenic long non-coding RNA UCA1 in acute myeloid leukemia

摘要: // James M. Hughes 1 , Ivano Legnini Beatrice Salvatori 1, 6 Silvia Masciarelli 2 Marcella Marchioni 3 Francesco Fazi Mariangela Morlando Irene Bozzoni 3, 4, 5 Alessandro Fatica Department of Biology and Biotechnology “C. Darwin”, Sapienza University Rome, Italy Anatomical, Histological, Forensic & Orthopaedic Sciences, Institute Biology, Molecular Medicine Nanobiotechnology, CNR, 4 Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Pasteur Fondazione Cenci-Bolognetti, Systems Herbert Irving Comprehensive Cancer Center, Columbia Medical New York, NY, USA Correspondence to: Fatica, e-mail: alessandro.fatica@uniroma1.it Keywords: long non-coding RNA, acute myeloid leukemia, CEBPA, UCA1 Received: February 05, 2015      Accepted: May 13, Published: 25, 2015 ABSTRACT Accumulating evidences indicate that different RNAs (lncRNAs) might play a relevant role in tumorigenesis, with their expression function already associated to cancer development progression. CCAAT/enhancer-binding protein-α (CEBPA) is critical regulator differentiation whose inactivation contributes the leukemia (AML). Mutations C/EBPα occur around 10% AML cases, leading 30-kDa dominant negative isoform (C/EBPα-p30). In this study, we identified oncogenic urothelial carcinoma (UCA1) lncRNA as novel target C/EBPα-p30. We show wild-type C/EBPα-p30 can bind promoter but have opposite effects on expression. While represses, induce transcription. Notably, also increases cytogenetically normal cases carrying biallelic CEBPA mutations. Furthermore, demonstrate sustains proliferation cells by repressing cell cycle p27 kip1 . Thus, identified, first time, an functioning concert AML.