Li Qun, Wang Jianmin
Department of PICU, First People's Hospital of Shangqiu City Henan Province China.
Department of Pediatric Medicine, First People's Hospital of Shangqiu City No. 292, Kaixuan Road, Yuyang District Shangqiu Henan Province 476100 China
RSC Adv. 2019 Sep 6;9(48):28126-28134. doi: 10.1039/c9ra04843j. eCollection 2019 Sep 3.
: Development of chemoresistance remains a major obstacle for pediatric acute myeloid leukemia (AML) management. Zinc finger antisense 1 (ZFAS1) is a novel tumor-related lncRNA that has been reported as an oncogene involved in the development of pediatric AML. The purpose of the present study was to investigate the role and underlying mechanism of ZFAS1 in AML chemoresistance. : The expression levels of ZFAS1 and miR-195 were assessed by qRT-PCR and Myb expression was detected using western blotting. The CCK-8 assay was used to determine the IC value for adriamycin (ADR) and cell proliferation. Cell apoptosis was measured by flow cytometry. The targeted interaction between miR-195 and ZFAS1 or Myb was evaluated by the dual-luciferase reporter assay or RNA immunoprecipitation assay. : Our data revealed that ADR treatment induced ZFAS1 expression in pediatric AML. Silencing of ZFAS1 or Myb alleviated AML cell resistance to ADR . ZFAS1 directly targeted miR-195 and negatively modulated miR-195 expression. Myb was a direct target of miR-195. Moreover, the inhibitory effect of ZFAS1 silencing on ADR resistance of AML cells was mediated by miR-195 . Myb was involved in the regulation of the ZFAS1/miR-195 axis in ADR resistance of AML cells. : Our data indicated that ZFAS1 silencing alleviated ADR resistance of AML cells through acting as a sponge for miR-195 and regulating Myb expression. Targeting ZFAS1 might be a promising therapeutic strategy for pediatric AML treatment.
化疗耐药的产生仍然是小儿急性髓系白血病（AML）治疗的主要障碍。锌指反义1（ZFAS1）是一种新型的肿瘤相关长链非编码RNA，已被报道为参与小儿AML发生发展的致癌基因。本研究的目的是探讨ZFAS1在AML化疗耐药中的作用及潜在机制。通过qRT-PCR评估ZFAS1和miR-195的表达水平，使用蛋白质免疫印迹法检测Myb表达。采用CCK-8法测定阿霉素（ADR）的IC值和细胞增殖情况。通过流式细胞术检测细胞凋亡。采用双荧光素酶报告基因检测法或RNA免疫沉淀检测法评估miR-195与ZFAS1或Myb之间的靶向相互作用。我们的数据显示，ADR处理可诱导小儿AML中ZFAS1的表达。沉默ZFAS1或Myb可减轻AML细胞对ADR的耐药性。ZFAS1直接靶向miR-195并负向调节miR-195的表达。Myb是miR-195的直接靶点。此外，ZFAS1沉默对AML细胞ADR耐药性的抑制作用是由miR-195介导的。Myb参与了AML细胞ADR耐药中ZFAS1/miR-195轴的调控。我们的数据表明，ZFAS1沉默通过充当miR-195的海绵并调节Myb表达来减轻AML细胞的ADR耐药性。靶向ZFAS1可能是小儿AML治疗的一种有前景的治疗策略。
