Research Paper Volume 13, Issue 9 pp 13179—13194

C/EBPα is indispensable for PML/RARα-mediated suppression of long non-coding RNA NEAT1 in acute promyelocytic leukemia cells

Doudou Tang1, , Piao Hu2,3, , Dengqin Zhu2,3, , Yujiao Luo2,3, , Mingjie Chen4, , Guangsen Zhang2,3, , Yewei Wang2,3, ,

  • 1 Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Hunan Centre for Evidence-Based Medicine, Central South University, Changsha, Hunan, China
  • 2 Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
  • 3 Institute of Molecular Hematology, Central South University, Changsha, Hunan, China
  • 4 Cloud-Seq Bio-Tech Inc., Shanghai, China

Received: September 5, 2020       Accepted: March 27, 2021       Published: April 26, 2021
How to Cite

Copyright: © 2021 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Better understanding of the transcriptional regulatory network in acute promyelocytic leukemia (APL) cells is critical to illustrate the pathogenesis of other types of acute myeloid leukemia. Previous studies have primarily focused on the retinoic acid signaling pathway and how it is interfered with by promyelocytic leukemia/retinoic acid receptor-α (PML/RARα) fusion protein. However, this hardly explains how APL cells are blocked at the promyelocytic stage. Here, we demonstrated that C/EBPα bound and transactivated the promoter of long non-coding RNA NEAT1, an essential element for terminal differentiation of APL cells, through C/EBP binding sites. More importantly, PML/RARα repressed C/EBPα-mediated transactivation of NEAT1 through binding to NEAT1 promoter. Consistently, mutation of the C/EBP sites or deletion of retinoic acid responsive elements (RAREs) and RARE half motifs abrogated the PML/RARα-mediated repression. Moreover, silencing of C/EBPα attenuated ATRA-induced NEAT1 upregulation and APL cell differentiation. Finally, simultaneous knockdown of C/EBPα and C/EBPβ reduces ATRA-induced upregulation of C/EBPε and dramatically impaired NEAT1 activation and APL cell differentiation. In sum, C/EBPα binds and transactivates NEAT1 whereas PML/RARα represses this process. This study describes an essential role for C/EBPα in PML/RARα-mediated repression of NEAT1 and suggests that PML/RARα could contribute to the pathogenesis of APL through suppressing C/EBPα targets.


APL: acute promyelocytic leukemia; AML: acute myeloid leukemia; PML/RARα: promyelocytic leukemia/retinoic acid receptor-α; ATRA: all-trans retinoic acid; lncRNA: long non-coding RNA; NEAT1: nuclear enriched abundant transcript 1; RARE: retinoic acid responsive element; ChIP: chromatin immunoprecipitation.