期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 32, 期 6, 页码 1818-1829出版社
KARGER
DOI: 10.1159/000356615
关键词
As2O3; Acute promyelocytic leukemia; Apoptosis; microRNA; PML
资金
- National Basic Research Program of China (973 program) [2013CB531104]
- Funds for Creative Research Groups of the National Natural Science Foundation of China [81121003]
- National Natural Science Foundation of China [31171094, 31300943]
- Postgraduate Research Innovation Fund of Heilongjiang [YJSCX2012-243HLJ]
Background: Arsenic trioxide (As2O3), an ancient drug used in traditional Chinese medicine, has substantial anticancer activities, especially in the treatment of patients suffering from acute promyelocytic leukemia (APL); however the underlying mechanisms are not well understood. Methods: MTT assay was used to detect the cell viability. Flow Cytometry analysis and caspase-3 activity assay were used to measure apoptosis of APL cells. Caspase-3 and Bax levels were analyzed by western blot and let-7d and miR-766 levels were determined by real-time RT-PCR. Results: As2O3 significantly inhibited cell viability and induced apoptosis in APL cells. Several microRNAs, including let-7d and miR-766, were dysregulated in APL cells treated with As2O3. The expression of caspase-3 and Bax, which are targets of let-7d and miR766, respectively, were up-regulated in As2O3 treated cells. Transfection of let-7d and miR-766 into NB4 cells decreased the expression of caspase-3 and Bax, respectively. Correspondingly, transfection of these microRNAs increased NB4 cell viability. As2O3 induced degradation of promyelocytic leukemia (PML), and then induced the down-regulation of both let-7d and miR-766 in NB4 cells. Conclusions: We construct a dysregulated microRNA network involved in As2O3-induced apoptosis in APL. Targeting this network may be a new strategy for the prevention of side effects associated with APL treatment with As2O3. Copyright (C) 2013 S. Karger AG, Basel
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