miR-483-5p decreases the radiosensitivity of nasopharyngeal carcinoma cells by targeting DAPK1
miR-483-5p decreases the radiosensitivity of nasopharyngeal carcinoma cells by targeting DAPK1
复制标题
miR-483-5p通过靶向DAPK1降低鼻咽癌细胞的放射敏感性
DOI：
10.1038/s41374-018-0169-6
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发表时间：
2019-05-01
影响因子：
5
通讯作者：
Yuan, Yawei
中科院分区：
文献类型：
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作者：
Tian, Yunhong;Yan, Miaohong;Yuan, Yawei
放射抵抗导致的复发或转移是鼻咽癌治疗面临的主要挑战。大量证据支持miRNAs的异常表达在放射抵抗和恶性肿瘤中的作用。在某些癌症中，miR-483- 5 p与较差的疾病特异性生存期相关。因此，我们研究了miR-483- 5 p在鼻咽癌放射敏感性中的作用以及miR-483- 5 p影响鼻咽癌细胞放射敏感性的机制。在这项研究中，我们发现miR-483- 5 p的过表达降低了鼻咽癌细胞在体外和体内的放射敏感性。从机制上讲，miR-483- 5 p通过靶向死亡相关蛋白激酶1（DAPK 1）减少辐射诱导的细胞凋亡和DNA损伤，并增加NPC细胞集落形成来发挥这些功能。最后，我们的结果证实，miR-483- 5 p的上调与NPC患者的晚期临床分期和较低的总生存期相关。这些发现为我们理解NPC治疗失败的分子机制提供了新的见解。调节miR-483- 5 p和DAPK 1水平可能为增加这些肿瘤的放射敏感性提供新的方法。
Recurrence or metastasis resulting from radioresistance are the main challenges for the treatment of nasopharyngeal carcinoma (NPC). A great deal of evidence supports the role of abnormal expression of miRNAs in radioresistance and malignancy. In some cancers, miR-483-5p is associated with inferior disease-specific survival. Therefore, we investigated the role of miR-483-5p in NPC radiosensitivity and the mechanism by which the miR-483-5p affects the radiosensitivity of NPC cells. In this study, we show that the overexpression of miR-483-5p decreases the radiosensitivity of NPC cells in vitro and in vivo. Mechanistically, miR-483-5p exerts these functions by decreasing radiation-induced apoptosis and DNA damage, and by increasing NPC cell colony formation, via targeting death-associated protein kinase 1 (DAPK1). Finally, our results confirm that the upregulation of miR-483-5p is correlated with advanced clinical stage and inferior overall survival of patients with NPC. These findings provide novel insights into our understanding of the molecular mechanisms underlying therapy failure in NPC. Modulation of miR-483-5p and DAPK1 levels may provide a new approach for increasing the radiosensitivity of these tumors.