RESUMO
Circular RNAs (circRNAs) are a class of newly identified noncoding RNA and are considered as a new feature of eukaryotic gene expression. Hundreds of thousands of endogenous circRNAs have been found in mammalian cells, which we knew little before. CircRNAs are covalently closed, circular RNA molecules that typically comprise exonic sequences and are spliced at canonical splice sites. Researchers with RNA-Seq technology have identified that the expression of circRNAs is developmentally regulated, tissue- and cell-type specific. Like long noncoding RNAs (lncRNAs), circRNAs are becoming a new research hotspot in the RNA field, and aberrant expression of circRNAs could contribute to carcinogenesis. Recent studies have demonstrated that circRNAs play important roles in the development, maintenance, and progression of leukemia. Herein, we describe the biologic characteristics and functions of circRNAs, with a focus on circRNAs that play essential roles in leukemia.
Assuntos
Leucemia/genética , RNA Circular/genética , Animais , Biomarcadores Tumorais/metabolismo , Hematopoese/genética , Humanos , Modelos Biológicos , Terminologia como AssuntoRESUMO
Emerging evidences have shown that long non-coding RNAs (lncRNAs) play critical roles in cancer development and cancer therapy. LncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) is indispensable during acute promyelocytic leukemia (APL) cell differentiation induced by all-trans retinoic acid (ATRA). However, the precise mechanism of NEAT1 upregulation has not been fully understood. In this study, we performed chromatin immunoprecipitation and luciferase reporter assays to demonstrate that C/EBP family transcription factor C/EBPß bind to and transactivate the promoter of lncRNA NEAT1 through the C/EBPß binding sites both around -54 bp and -1453 bp upstream of the transcription start site. Moreover, the expression of C/EBPß was increased after ATRA treatment, and the binding of C/EBPß in the NEAT1 promoter was also dramatically increased. Finally, knockdown of C/EBPß significantly reduced the ATRA-induced upregulation of NEAT1. In conclusion, C/EBPß directly activates the expression of NEAT1 through binding to the promoter of NEAT1. Knockdown of C/EBPß impairs ATRA-induced transcriptional activation of NEAT1. Our data indicate that C/EBPß contributes to ATRA-induced activation of NEAT1 during APL cell differentiation. Our results enrich our knowledge on the regulation of lncRNAs and the regulatory role of C/EBPß in APL cell differentiation.
