Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663
Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663
复制标题
视黄酸通过上调 miR-663 诱导 HL-60 细胞分化
DOI：
10.1186/1756-8722-4-20
复制
发表时间：
2011-04-25
影响因子：
28.5
通讯作者：
Jian, Ni
中科院分区：
文献类型：
--
作者：
Jian, Pan;Li, Zhao Wen;Jian, Ni
背景：全反式维甲酸(ATRA)可诱导急性髓系白血病(AML)细胞系HL-60分化，但其调控机制尚未完全阐明。方法利用生物信息学和体外实验，我们鉴定了ATRA诱导粒细胞分化过程中HL-60细胞的microRNA基因表达谱。结果ATRA可上调6个microRNA，miR-663、miR-494、miR-145、miR-22、miR-363*和miR-223，而miR-10a、miR-181和miR-612下调。此外，miR-663的表达受ATRA的调节。由于巨细胞病毒(CMV)启动子在某些淋巴细胞中无效，我们使用含有脾病灶形成病毒(SFFV-F)启动子的慢病毒(LV)骨架来驱动miR-663的表达。结论MIR-663在全反式维甲酸诱导HL-60细胞分化过程中可能起重要作用。慢病毒载体miR-663有可能直接用于血液系统恶性肿瘤的抗癌治疗
BackgroundDifferentiation of the acute myeloid leukemia (AML) cell line HL-60 can be induced by all trans-retinoic acid (ATRA); however, the mechanism regulating this process has not been fully characterized.MethodsUsing bioinformatics andin vitroexperiments, we identified the microRNA gene expression profile of HL-60 cells during ATRA induced granulocytic differentiation.ResultsSix microRNAs were upregulated by ATRA treatment, miR-663, miR-494, miR-145, miR-22, miR-363* and miR-223; and three microRNAs were downregulated, miR-10a, miR-181 and miR-612. Additionally, miR-663 expression was regulated by ATRA. We used a lentivirus (LV) backbone incorporating the spleen focus forming virus (SFFV-F) promoter to drive miR-663 expression, as the CMV (Cytomegalovirus) promoter is ineffective in some lymphocyte cells. Transfection of LV-miR-663 induced significant HL-60 cell differentiationin vitro.ConclusionsOur results show miR-663 may play an important role in ATRA induced HL-60 cell differentiation. Lentivirus delivery of miR-663 could potentially be used directly as an anticancer treatment in hematological malignancies