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Published on: September 1, 2019
Inhibition of long non-coding RNA NEAT1 impairs myeloid differentiation in acute promyelocytic leukemia cells
1Institute of Hematology, Medical College, Jinan University, Guangzhou 510632, China. yangqiuli@hotmail.com.
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.
Insights
Reduced expression of nuclear enriched abundant transcript 1 (NEAT1), a long non-coding RNA, is observed in acute promyelocytic leukemia (APL). NEAT1 is crucial for myeloid differentiation and its repression by PML-RARα may contribute to APL pathogenesis.
Area of Science:
- Molecular biology
- Cancer research
- Epigenetics
Background:
- Acute promyelocytic leukemia (APL) is driven by the PML-RARα fusion protein.
- The oncogenic mechanisms of PML-RARα and the role of long non-coding RNAs (lncRNAs) in APL are not fully understood.
Purpose of the Study:
- To investigate the role of the lncRNA NEAT1 in APL.
- To determine the relationship between NEAT1 expression, PML-RARα, and myeloid differentiation in APL.
Main Methods:
- NEAT1 expression was quantified in APL samples and cell lines using qRT-PCR.
- PML-RARα levels were assessed by Western blot.
- Myeloid differentiation was evaluated by CD11b expression via flow cytometry and ATRA-induced differentiation was monitored after NEAT1 knockdown using siRNA.
Main Results:
- NEAT1 expression is significantly repressed in de novo APL samples compared to healthy donors.
- PML-RARα was found to repress NEAT1 expression.
- NEAT1 expression increased during ATRA-induced differentiation of NB4 cells, and NEAT1 knockdown inhibited this differentiation, highlighting its importance in myeloid differentiation.
Conclusions:
- Reduced NEAT1 expression may contribute to the pathogenesis of APL by impairing myeloid differentiation.
- NEAT1 is a critical regulator of myeloid differentiation in APL cells.
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