Let-7 g microRNA sensitizes fluorouracil-resistant human hepatoma cells

Let-7 g microRNA sensitizes fluorouracil-resistant human hepatoma cells
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Let-7 g microRNA 致敏耐氟尿嘧啶的人肝癌细胞

DOI:
10.1691/ph.2014.3849
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发表时间:
2014-04-01
期刊:
影响因子:
1.6
通讯作者:
Lei, Xiaoyong
Lei, Xiaoyong
中科院分区:
医学4区
文献类型:
--
作者:
Tang, Huifang;Zhang, Pengfei;Lei, Xiaoyong

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Let-7 microRNA在多种人类肿瘤中表达较低,参与肿瘤的发生。本研究探讨let-7 g microRNA对人肝癌细胞系Bel-7402/5-Fu耐药细胞中HMGA 2基因表达的抑制作用,以及let-7 g microRNA对Bel-7402/5-Fu耐药细胞药物敏感性的影响。构建Let-7 g microRNA和阴性microRNA质粒,瞬时转染Bel-7402/5-Fu细胞。与阴性microRNA转染子和未处理的细胞相比,microRNA瞬时转染子中HMGA 2 mRNA和蛋白的表达水平明显降低。流式细胞术显示let-7 g microRNA细胞中S期增加。二甲基噻唑-溴化二苯基四唑(MU)结果表明,在用0.13-13 μ g/ml 5-Fu处理后,microRNA转染子具有比阴性载体或未处理的细胞更高的细胞抑制率。结果表明,let-7 g microRNA能增强5-Fu对人肝癌细胞周期的抑制作用,并使细胞对5-Fu敏感,从而提高5-Fu治疗肝癌的疗效。
Let-7 microRNA is expressed in lower lever in a variety of human tumors and is involved in tumorigenesis. This study investigated the inhibitory effect of the let-7 g microRNA on the expression of the HMGA2 gene in the fluorouracil (5-Fu)-resistant human hepatoma cell line Bel-7402/5-Fu, and the effect of let-7 g microRNA on drug sensitization in Bel-7402/5-Fu cells. Let-7 g microRNA and negative microRNA plasmids were constructed and transient transfected into Bel-7402/5-Fu cells. Expression levels of HMGA2 mRNA and protein in microRNA transient transfectants were clearly reduced as compared with negative microRNA transfectants and untreated cells. Flow cytometry revealed increased in S phase in let-7 g microRNA cells. dimethylthiazol-diphenyltetrazolium bromide (MU) results indicated that microRNA transfectants had a higher cell inhibition rate than the negative vector or untreated cells after treatment with 0.13-13 mu g/ml 5-Fu. In addition, cyclinA was down-regulated in the let-7 g transfectants cells.The results showed that let-7 g microRNA contributed to an increase of 5-Fu-induced cell cycle inhibit in human hepatoma cell and sensitized cells to 5-Fu, leading to increased the effectiveness of the drug in treating hepatoma cancer.