miR-873 acts as a novel sensitizer of glioma cells to cisplatin by targeting Bcl-2
miR-873 acts as a novel sensitizer of glioma cells to cisplatin by targeting Bcl-2
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miR-873通过靶向Bcl-2作为神经胶质瘤细胞对顺铂的新型敏化剂
DOI：
10.3892/ijo.2015.3143
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发表时间：
2015-10-01
影响因子：
5.2
通讯作者：
He, Xiaohua
中科院分区：
文献类型：
--
作者：
Chen, Xiong;Zhang, Yingying;He, Xiaohua
顺铂是一种常用于胶质瘤患者的化疗药物，常导致化疗耐药性。越来越多的证据表明microRNAs（miRNAs）与胶质瘤的耐药性有关。然而，miR-873在胶质瘤顺铂耐药中的功能仍然未知。在这项研究中，我们发现，包括miR-873在内的许多miRNA在顺铂耐药胶质瘤细胞中的表达与野生型胶质瘤细胞相比存在差异。此外，顺铂以时间依赖性方式降低miR-873的表达。过表达miR-873可降低顺铂耐药胶质瘤细胞的增殖、迁移和侵袭能力，增加顺铂耐药胶质瘤细胞的凋亡，使其对顺铂诱导的细胞生长停滞和凋亡敏感。此外，与7例正常脑组织相比，12例高级别胶质瘤患者的组织中miR-873下调，而Bcl-2上调，并且miR-873水平与Bcl-2蛋白水平呈负相关。荧光素酶报告基因测定进一步证实了Bcl-2是miR-873的直接靶点，并且miR-873降低了顺铂耐药胶质瘤细胞中Bcl-2蛋白的水平。值得注意的是，Bcl-2的再表达减弱了顺铂耐药胶质瘤细胞中miR-873的功能和细胞对顺铂的敏感性。综上所述，这些数据表明miR-873可能是顺铂耐药性的潜在标志物，也是顺铂治疗中有希望的增敏剂。
Treatment with cisplatin, a chemotherapeutic agent commonly used in glioma patients, often results in chemoresistance. Increasing evidence has shown that microRNAs (miRNAs) are implicated in the drug resistance of gliomas. However, the function of miR-873 in cisplatin resistance of gliomas remains unknown. In this study, we found that many miRNAs, including miR-873, are differentially expressed in cisplatin-resistant glioma cells compared to wild-type glioma cells. Moreover, cisplatin reduced the expression of miR-873 in a time-dependent manner. Overexpression of miR-873 decreased the cell proliferation, migration and invasion while increased apoptosis of cisplatin-resistant glioma cells and sensitized the cells to cisplatin-induced cell growth arrest and apoptosis. Furthermore, miR-873 was downregulated while Bcl-2 was upregulated in the tissues of twelve high-grade glioma patients compared to seven normal brain tissues, and the miR-873 level was negatively correlated with the Bcl-2 protein level. A luciferase reporter assay further confirmed that Bcl-2 was a direct target of miR-873, and miR-873 decreased the level of the Bcl-2 protein in cisplatin-resistant glioma cells. Notably, re-expression of Bcl-2 attenuated the function of miR-873 in cisplatin-resistant glioma cells and the sensitivity of the cells to cisplatin. Taken together, these data suggest that miR-873 might be a potential marker for cisplatin resistance and a promising sensitizer in cisplatin treatment.