Inhibition of long non-coding RNA NEAT1 impairs myeloid differentiation in acute promyelocytic leukemia cells

Abstract

BackgroundAcute 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.MethodsWe 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.ResultsWe 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.ConclusionsOur results indicate that reduced expression of the nuclear long noncoding RNA NEAT1 may play a role in the myeloid differentiation of APL cells.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-693) contains supplementary material, which is available to authorized users.

Overexpression of lncRNA NEAT1 mitigates multidrug resistance by inhibiting ABCG2 in leukemia

“…However, downregulation of NEAT1 has been observed in the several other malignancies, including those affecting the liver, retina and esophagus (37). Furthermore, anomalous NEAT1 expression has been reported in various human malignancies, including acute promyelocytic leukemia, where NEAT1 repression was predominant in patients with leukemia caused by promyelocytic leukemia-retinoic acid receptor α (RARα) gene translocation (17). In addition, time-lapse imaging experiments with NEAT1 constructs demonstrated the integral role of NEAT1 expression and paraspeckles formation at the NEAT1 locus (38).…”

“…A previous study by Zeng et al reported that NEAT1 lncRNA is comprised of two isoforms, NEAT1_1 and NEAT1_2 (17). Therefore, the present study compared conservative sequences of the two isoforms using rVista 2.0 (http://rvista.dcode.org/) by performing evolutionary analysis of transcription factor binding sites.…”

Molecular and cellular aspects of extramedullary manifestations of acute myeloid leukemia

“…[16] This fusion protein causes a block at the promyelocytic differentiation stage. [17] APL can occur in extramedullary form, and EMI is responsible for 3-8% of cases in relapse. The most common target tissues are CNS and skin.…”

Upregulation and Clinicopathological Significance of Long Non-coding NEAT1 RNA in NSCLC Tissues

“…This lncRNA has been recently revealed to be an architectural component of a subnuclear structure called the paraspeckle, which is suggested to be involved in regulating gene expression by retaining mRNAs for editing in the nucleus (Chen and Carmichael, 2009). Anomalous NEAT1 expression has been reported in human malignancies, including of leukemia and ovarian carcinoma (Kim et al, 2010;Zeng et al, 2014). However, it is not yet fully understood how NEAT1 affects carcinogenesis and biological behavior of NSCLC.…”