microRNA expression alteration after arsenic trioxide treatment in HepG-2 cells
microRNA expression alteration after arsenic trioxide treatment in HepG-2 cells
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三氧化二砷处理 HepG-2 细胞后 microRNA 表达变化
DOI：
10.1111/j.1440-1746.2010.06317.x
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发表时间：
2011-01-01
影响因子：
4.1
通讯作者：
Liu, Lian-Xin
中科院分区：
文献类型：
--
作者：
Meng, Xian-Zhi;Zheng, Tong-Sen;Liu, Lian-Xin
背景与目的：越来越多的微小RNA（miRNA）被发现参与肿瘤的发生和发展。多年来，三氧化二砷一直是癌症治疗中有效的化疗药物。在本研究中，我们旨在寻找参与三氧化二砷治疗癌症机制的miRNA。方法：通过miRNA微阵列和定量实时聚合酶链反应检测miRNA的表达谱。通过细胞活力测定、流式细胞术分析、miRNA靶标预测、Western blot分析和荧光素酶报告基因测定来确定一种选定的miRNA（即mir-29a）对HepG-2细胞生物学行为的影响。结果：在芯片中的677个人类miRNA中，与对照组相比，三氧化二砷处理的HepG-2细胞中5个miRNA上调，4个下调。如果仅考虑两倍以上的变化，则鉴定出四种miRNA，即miR-24、miR-29a、miR-30a和miR-210，它们均被上调。其中，miR-29a通过抑制细胞生长、诱导细胞凋亡在肝癌细胞中表现出积极的治疗作用，并且PPM1D被证实是miR-29a的靶基因。此外，还检测到miR-29a和三氧化二砷之间存在协同效应。结论：三氧化二砷改变了HepG-2细胞中的miRNA表达谱。在改变的 miRNA 中，miR-29a 似乎在三氧化二砷治疗肝癌的机制中发挥了作用。 miR-29a和三氧化二砷之间的协同作用可能会降低其剂量和毒副作用，从而为该药物在癌症治疗中提供新的机会。
Background and Aim:More and more microRNA (miRNA) are found to be involved in tumor genesis and progress. Arsenic trioxide has been an effective chemotherapeutic drug in cancer therapy for many years. In this study, we aimed to find the miRNA involved in the mechanisms of arsenic trioxide treatment in cancer therapy.Methods:We detected the expression profile of miRNA by miRNA microarray and quantitative real-time polymerase chain reaction. Cell viability assay, flow cytometry analysis, prediction of miRNA targets, Western blot analysis and luciferase reporter assay were carried out to determine the role of one selected miRNA, namely mir-29a, in affecting the biological behaviors of HepG-2 cells.Results:Among the 677 human miRNA in the microarray, five miRNA were upregulated and four were downregulated in HepG-2 cells treated with arsenic trioxide compared to their controls. If only changes above two folds were considered, four miRNA were identified, namely miR-24, miR-29a, miR-30a and miR-210, which were all upregulated. Among them, miR-29a showed a positive therapeutic effect in liver cancer cells by inhibiting cell growth and inducing cell apoptosis, and PPM1D was confirmed to be the target gene of miR-29a. Furthermore, a synergy effect was detected between miR-29a and arsenic trioxide.Conclusions:Arsenic trioxide altered miRNA expression profile in HepG-2 cells. Among the altered miRNA, miR-29a seemed to take a role in the mechanism of arsenic trioxide in liver cancer therapy. The synergy effect between miR-29a and arsenic trioxide may offer this drug a new chance in cancer therapy by decreasing its dose and toxic side-effects.