title: Inhibition of long non-coding RNA NEAT1 impairs myeloid differentiation in acute promyelocytic leukemia cells.
abstract: BACKGROUND
  Acute promyelocytic leukemia (APL) is characterized by the reciprocal translocation t(15;17), which fuses PML with retinoic acid receptor alpha (RARα). Although PML-RARα is crucially important for pathogenesis and responsiveness to treatment, the molecular and cellular mechanisms by which PML-RARα exerts its oncogenic potential have not been fully elucidated. Recent reports have suggested that long non-coding RNAs (lncRNAs) contribute to the precise control of gene expression and are involved in human diseases. Little is known about the role of lncRNA in APL.
  
  
  METHODS
  We analyzed NEAT1 expression in APL samples and cell lines by real-time quantitative reverse transcription-PCR (qRT-PCR). The expression of PML-RARα was measured by Western blot. Cell differentiation was assessed by measuring the surface CD11b antigen expression by flow cytometry analysis.
  
  
  RESULTS
  We found that nuclear enriched abundant transcript 1 (NEAT1), a lncRNA essential for the formation of nuclear body paraspeckles, is significantly repressed in de novo APL samples compared with those of healthy donors. We further provide evidence that NEAT1 expression was repressed by PML-RARα. Furthermore, significant NEAT1 upregulation was observed during all-trans retinoic acid (ATRA)-induced NB4 cell differentiation. Finally, we demonstrate the importance of NEAT1 in myeloid differentiation. We show that reduction of NEAT1 by small interfering RNA (siRNA) blocks ATRA-induced differentiation.
  
  
  CONCLUSIONS
  Our results indicate that reduced expression of the nuclear long noncoding RNA NEAT1 may play a role in the myeloid differentiation of APL cells.
authors.forename: Chengwu
authors.initials: C
authors.lastname: Zeng
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Xibao
authors.initials: X
authors.lastname: Yu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cheng
authors.forename: Lijian
authors.initials: L
authors.lastname: Yang
authors.forename: Shaohua
authors.initials: S
authors.lastname: Chen
authors.affiliation: Institute of Hematology, Medical College, Jinan University, Guangzhou 510632, China. yangqiuli@hotmail.com.
authors.forename: Yangqiu
authors.initials: Y
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D045744:Cell Line, Tumor; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology; D055815:Young Adult
chemical_list: C577276:NEAT1 long non-coding RNA, human; D015514:Oncogene Proteins, Fusion; D062085:RNA, Long Noncoding; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin