miRNA-378 reverses chemoresistance to cisplatin in lung adenocarcinoma cells by targeting secreted clusterin.
miRNA-378 reverses chemoresistance to cisplatin in lung adenocarcinoma cells by targeting secreted clusterin.
复制标题
miRNA-378 通过靶向分泌的凝聚素来逆转肺腺癌细胞对顺铂的化疗耐药性。
DOI：
10.1038/srep19455
复制
发表时间：
2016-01-19
影响因子：
4.6
通讯作者：
Cai L
中科院分区：
文献类型：
--
作者：
Chen X;Jiang Y;Huang Z;Li D;Chen X;Cao M;Meng Q;Pang H;Sun L;Zhao Y;Cai L
顺铂耐药是非小细胞肺癌治疗的主要障碍，其机制尚未完全阐明。本研究的目的是确定miR-378在肺腺癌细胞对顺铂（cDDP）敏感性中的作用及其工作机制。通过TargetScan和荧光素酶测定，发现miR-378直接靶向sCLU。在A549/cDDP和Anip 973/cDDP细胞中调节miR-378和sCLU，以研究miR-378对cDDP敏感性和凋亡作用的影响。在裸鼠异种移植模型中分析miR-378上调对肿瘤生长的影响。在患者样品中测试miR-378与化学抗性之间的相关性。我们发现，在A549/cDDP和Anip 973/cDDP细胞中上调miR-378显著下调sCLU表达，并使这些细胞对cDDP敏感。miR-378过表达抑制异种移植动物模型中的肿瘤生长和sCLU表达。对人肺腺癌组织的分析显示，cDDP敏感组表达较高水平的miR-378和较低水平的sCLU。miR-378与sCLU呈负相关。总之，我们将sCLU鉴定为新的miR-378靶点，并且我们表明通过miR-378靶向sCLU可能有助于使肺腺癌细胞中对顺铂的化学抗性失效。
Cisplatin resistance is a major obstacle in the treatment of NSCLC, and its mechanism has not been fully elucidated. The objectives of the study were to determine the role of miR-378 in the sensitivity of lung adenocarcinoma cells to cisplatin (cDDP) and its working mechanism. With TargetScan and luciferase assay, miR-378 was found to directly target sCLU. miR-378 and sCLU were regulated in A549/cDDP and Anip973/cDDP cells to investigate the effect of miR-378 on the sensitivity and apoptotic effects of cDDP. The effect of miR-378 upregulation on tumor growth was analyzed in a nude mouse xenograft model. The correlation between miR-378 and chemoresistance was tested in patient samples. We found that upregulation of miR-378 in A549/cDDP and Anip973/cDDP cells significantly down-regulated sCLU expression, and sensitized these cells to cDDP. miR-378 overexpression inhibited tumor growth and sCLU expression in a xenograft animal model. Analysis of human lung adenocarcinoma tissues revealed that the cDDP sensitive group expressed higher levels of miR-378 and lower levels of sCLU. miR-378 and sCLU were negatively correlated. To conclude, we identified sCLU as a novel miR-378 target, and we showed that targeting sCLU via miR-378 may help disable the chemoresistance against cisplatin in lung adenocarcinoma cells.