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The c‐Myc‐regulated miR‐17‐92 cluster mediates ATRA‐induced APL cell differentiation
Author(s) -
Yu Xibao,
Hu Yanyun,
Wu Yifan,
Fang Chunsheng,
Lai Jing,
Chen Shaohua,
Li Yangqiu,
Zeng Chengwu,
Zeng Yixin
Publication year - 2019
Publication title -
asia‐pacific journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 29
eISSN - 1743-7563
pISSN - 1743-7555
DOI - 10.1111/ajco.13225
Subject(s) - acute promyelocytic leukemia , flow cytometry , retinoic acid , microrna , cellular differentiation , downregulation and upregulation , cluster of differentiation , microbiology and biotechnology , cancer research , biology , cell , cell growth , apoptosis , cell culture , promyelocytic leukemia protein , chemistry , gene , biochemistry , genetics
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.