The c-Myc-regulated miR-17-92 cluster mediates ATRA-induced APL cell differentiation.
Asia Pac J Clin Oncol
; 15(6): 364-370, 2019 Dec.
Article
in En
| MEDLINE
| ID: mdl-31264378
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leukemia, Promyelocytic, Acute
/
Cell Differentiation
/
Proto-Oncogene Proteins c-myc
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MicroRNAs
Limits:
Humans
Language:
En
Journal:
Asia Pac J Clin Oncol
Year:
2019
Document type:
Article