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Published on: February 21, 2018
miR-139-5p Regulates the Proliferation of Acute Promyelocytic Leukemia Cells by Targeting MNT
Yueyue Fu1, Limin Li2, Jinxiao Hou1
1Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang, China.
Abstract:
Acute promyelocytic leukemia (APL) patients with progressive leukocytosis are more likely to have various complications and poor outcomes. However, the regulatory roles of microRNAs in the leukocytosis of APL have not been clarified. Our study aims to evaluate the effects of miRNAs on leukocytosis during induction therapy of APL patients and explore its potential mechanisms. During induction treatment, patients with white blood cell count higher than 10 × 109/L were divided into leukocytosis group and others were nonleukocytosis group. Using microarray assays, we found that miR-139-5p was significantly downregulated in the leukocytosis group. Elevated expression of miR-139-5p inhibited the proliferation of NB4 cells by arresting the cell cycle and inducing apoptosis. We further identified that MNT was a target of miR-139-5p. miR-139-5p significantly inhibited the proliferation, invasion, and migration function of NB4 cells through targeting MNT. Strategies for regulating miR-139-5p or MNT expression might provide new therapeutic approaches for progressive leukocytosis in APL.
Insights
MicroRNAs regulate white blood cell counts in acute promyelocytic leukemia (APL). Downregulated miR-139-5p is linked to leukocytosis, and restoring its levels may offer new APL treatment strategies.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Progressive leukocytosis in acute promyelocytic leukemia (APL) correlates with poor outcomes.
- The specific microRNA (miRNA) roles in APL leukocytosis remain unclear.
Purpose of the Study:
- To investigate the impact of miRNAs on leukocytosis during APL induction therapy.
- To explore the underlying mechanisms of miRNA regulation in APL.
Main Methods:
- Patients undergoing induction therapy were categorized into leukocytosis and non-leukocytosis groups based on white blood cell counts.
- Microarray analysis was employed to identify differentially expressed miRNAs.
- In vitro studies using NB4 cells assessed the functional effects of miR-139-5p and its target MNT.
Main Results:
- miR-139-5p was significantly downregulated in APL patients with leukocytosis.
- Increased miR-139-5p expression suppressed NB4 cell proliferation via cell cycle arrest and apoptosis induction.
- MNT was identified as a direct target of miR-139-5p, mediating its effects on cell proliferation, invasion, and migration.
Conclusions:
- miR-139-5p plays a crucial role in controlling leukocytosis in APL.
- Targeting miR-139-5p or its downstream effector MNT presents a potential therapeutic avenue for managing progressive leukocytosis in APL.
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