MicroRNAs Contribute to Promyelocyte Apoptosis in As2O3-Treated APL Cells

作者：Liang, Haihai; Li, Xuelian; Wang, Lu; Yu, Shaonan; Xu, Zhidan; Gu, Yunyan; Pan, Zhenwei; Li, Tianyu; Hu, Meiyu; Cui, Hairong; Liu, Xue; Zhang, Ying; Xu, Chaoqian; Guo, Rui; Lu, Yanjie; Yang, Baofeng; Shan, Hongli^*

来源：Cellular Physiology and Biochemistry, 2013, 32(6): 1818-1829.

DOI：10.1159/000356615

• As2O3
• Acute promyelocytic leukemia
• Apoptosis
• microRNA
• PML

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.

• 出版日期2013
• 单位哈尔滨医科大学