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/EBP beta bind to and transactivate the promoter of lncRNA NEAT1 through the C/EBP beta binding sites both around -54 bp and -1453 bp upstream of the transcription start site. Moreover, the expression of C/EBP beta was increased after ATRA treatment, and the binding of C/EBP beta in the NEAT1 promoter was also dramatically increased. Finally, knockdown of C/EBP beta significantly reduced the ATRA-induced upregulation of NEAT1. In conclusion, C/EBP beta directly activates the expression of NEAT1 through binding to the promoter of NEAT1. Knockdown of C/EBP beta impairs ATRA-induced transcriptional activation of NEAT1. Our data indicate that C/EBP beta 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/EBP beta in APL cell differentiation. (C) 2017 Published by Elsevier Inc.