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Published on: May 4, 2017
The c-Myc-regulated miR-17-92 cluster mediates ATRA-induced APL cell differentiation
Xibao Yu1,2, Yanyun Hu2, Yifan Wu2
1Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory Oncology in South China, Guangzhou, China.
Background:
Despite advances in the treatment of acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA), its underlying mechanism has not been fully elucidated. The oncogenic microRNA cluster miR-17-92 modulates multiple cellular processes, including survival, proliferation, and apoptosis. However, the role of miR-17-92 and its regulation has not yet been documented for APL.
Methods:
We analyzed miR-17-92 expression in APL samples and cell lines by qRT-PCR. The expression of c-Myc was measured by western blot. Cell differentiation was assessed by measuring the surface CD11b antigen expression by flow cytometry analysis.
Results:
We observed that miR-17-92 was upregulated in APL compared with healthy donors. Furthermore, we demonstrated that expressions of c-Myc and miR-17-92 are markedly suppressed during ATRA-induced NB4 cell differentiation. Importantly, we also demonstrated that miR-17-92 is directly regulated by c-Myc during the granulocytic differentiation of APL cells. Finally, the overexpression of miR-17-5p blocks ATRA-induced differentiation.
Conclusions:
We report abnormal expression of the miR-17-92 cluster in APL cells, which is responsible for the differentiation block in blast cells in APL. In addition, we identified miR-17-92 as a target gene of c-Myc during ATRA-induced granulocytic differentiation.
Insights
The miR-17-92 microRNA cluster is abnormally expressed in acute promyelocytic leukemia (APL) and blocks cell differentiation. This cluster is regulated by c-Myc during all-trans-retinoic acid treatment.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Acute promyelocytic leukemia (APL) treatment with all-trans-retinoic acid (ATRA) has advanced, but mechanisms remain unclear.
- The miR-17-92 microRNA cluster impacts cell survival, proliferation, and apoptosis.
- The role and regulation of miR-17-92 in APL are not well understood.
Purpose of the Study:
- To investigate the expression and role of the miR-17-92 cluster in APL.
- To explore the relationship between miR-17-92, c-Myc, and ATRA-induced differentiation in APL.
Main Methods:
- Quantitative reverse transcription PCR (qRT-PCR) to analyze miR-17-92 expression.
- Western blot to measure c-Myc expression.
- Flow cytometry to assess cell differentiation via CD11b antigen expression.
Main Results:
- miR-17-92 was upregulated in APL samples compared to healthy donors.
- c-Myc and miR-17-92 expression decreased during ATRA-induced differentiation of NB4 cells.
- miR-17-92 is directly regulated by c-Myc during APL cell differentiation.
- Overexpression of miR-17-5p inhibited ATRA-induced differentiation.
Conclusions:
- Abnormal miR-17-92 cluster expression contributes to the differentiation block in APL blast cells.
- miR-17-92 is identified as a c-Myc target gene during ATRA-induced granulocytic differentiation.
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