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

Abstract

Accumulating evidences indicate that different long non-coding RNAs (lncRNAs) might play a relevant role in tumorigenesis, with their expression and function already associated to cancer development and progression. CCAAT/enhancer-binding protein-α (CEBPA) is a critical regulator of myeloid differentiation whose inactivation contributes to the development of acute myeloid leukemia (AML). Mutations in C/EBPα occur in around 10% of AML cases, leading to the expression of a 30-kDa dominant negative isoform (C/EBPα-p30). In this study, we identified the oncogenic urothelial carcinoma associated 1 (UCA1) lncRNA as a novel target of the C/EBPα-p30. We show that wild-type C/EBPα and C/EBPα-p30 isoform can bind the UCA1 promoter but have opposite effects on UCA1 expression. While wild-type C/EBPα represses, C/EBPα-p30 can induce UCA1 transcription. Notably, we also show that UCA1 expression increases in cytogenetically normal AML cases carrying biallelic CEBPA mutations. Furthermore, we demonstrate that UCA1 sustains proliferation of AML cells by repressing the expression of the cell cycle regulator p27kip1. Thus, we identified, for the first time, an oncogenic lncRNA functioning in concert with the dominant negative isoform of C/EBPα in AML.

Long Non-Coding RNA Urothelial Carcinoma Associated 1 Promotes Proliferation, Migration and Invasion of Osteosarcoma Cells by Regulating microRNA-182

“…As non-coding RNA molecules in cells, lncRNAs participate in the regulation of multiple cell functions, such as cell proliferation, cell differentiation, cell migration and cell apoptosis [9]. Moreover, studies also demonstrate that lncRNAs play critical regulatory roles in a variety of disease processes, including neuro-degeneration and carcinogenesis [10,11] LncRNA urothelial carcinoma associated 1 (UCA1) has been aroused more and more attention in recent years due to its oncogenic/ tumor-suppressive roles in numerous cancer cells [12,13]. In terms of osteosarcoma, Li et al reported that overexpression of UCA1 promoted osteosarcoma initiation and progression [5].…”

A 4-lncRNA scoring system for prognostication of adult myelodysplastic syndromes

“…As lncRNAs have emerged as important participants in the pathogenesis and disease progression of AML, [66][67][68][69][70][71][72][73][74] it is likely that profiling of their expression would have significant impact on MDS prognostication. Recently, it has been shown that lncRNA expression signatures were closely associated with specific mutations and a small subset of lncRNAs could predict clinical outcome in cytogenetically normal elderly AML patients, 75 but the clinical significance of lncRNA profiling in MDSs has not yet been reported.…”

HCV infection, IFN response and the coding and non-coding host cell genome

“…and repressed by C/EBPα and miR-1 (Hughes et al, 2015;Wang et al, 2014c;Wu et al, 2013;Xue et al, 2014). It has been described that HCV-induced reactive oxygen species (ROS) inhibit C/EBPα activity and stabilize the expression of HIF-1α (Miura et al, 2008;Nishina et al, 2008).…”