Downregulation of miR-221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMP3 expression
Downregulation of miR-221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMP3 expression
复制标题
DOI：
10.1016/j.biopha.2015.12.002
复制
发表时间：
2016-02-01
影响因子：
7.5
通讯作者：
Chen, Yu
中科院分区：
文献类型：
--
作者：
Chen, Dan;Yan, Wangxiang;Chen, Yu
异常表达的微小RNA（miRNAs）参与口腔肿瘤发生，因为它们可以改变参与癌症进展的蛋白质的表达。目前还不清楚miRNA-221是否影响人口腔鳞癌细胞对阿霉素的耐药性。因此，我们研究了miR-221在口腔鳞状细胞癌细胞对化疗敏感性中的作用。用不同浓度的阿霉素处理Tca 8113和UM 2细胞。实时定量PCR（qRT-PCR）显示阿霉素处理Tca 8113和UM 2细胞后miR-221上调。通过使用miR-221抑制剂模拟物，我们发现耗尽miR-221的细胞增加了细胞对阿霉素的敏感性。在阿霉素处理的细胞中，miR-221的靶点金属蛋白酶组织抑制剂3（TIMP 3）的表达减少。TIMP 3耗竭逆转了miR-221抑制剂模拟物对细胞存活率和凋亡的影响。总之，这些结果表明，沉默miR-221通过上调TIMP 3表达增强人口腔鳞状细胞癌细胞对阿霉素的敏感性。(C)2015年Elsevier Masson SAS。All rights reserved.
Aberrantly expressed microRNAs (miRNAs) are involved in oral tumorigenesis since they can alter the expression of proteins involved in cancer progression. It remains unclear whether miRNA-221 influences the resistance of human oral squamous cell carcinoma cells to Adriamycin. We therefore investigated the role of miR-221 in the sensitivity of oral squamous cell carcinoma cells to chemotherapy. Tca8113 and UM2 cells were treated with different concentrations of Adriamycin. Quantitative real-time PCR (qRT-PCR) revealed miR-221 upregulation after Adriamycin treatment of Tca8113 and UM2 cells. By using miR-221 inhibitor mimics, we found that depleting cells of miR-221 increases the sensitivity of the cells to Adriamycin. The expression of tissue inhibitor of metalloproteinase-3 (TIMP3), a target of miR-221, was decreased in cells treated with Adriamycin. TIMP3 depletion reversed the effect of a miR-221 inhibitor mimics on cell survival rates and apoptosis. Together, these results reveal that silencing of miR-221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMP3 expression. (C) 2015 Elsevier Masson SAS. All rights reserved.