Regulation of autophagy by miR-30d impacts sensitivity of anaplastic thyroid carcinoma to cisplatin.
Regulation of autophagy by miR-30d impacts sensitivity of anaplastic thyroid carcinoma to cisplatin.
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DOI：
10.1016/j.bcp.2013.12.004
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发表时间：
2014-02-15
影响因子：
5.8
通讯作者：
Yang, J. M.
中科院分区：
文献类型：
--
作者：
Zhang, Y.;Yang, W. Q.;Zhu, H.;Qian, Y. Y.;Zhou, L.;Ren, Y. J.;Ren, X. C.;Zhang, L.;Liu, X. P.;Liu, C. G.;Ming, Z. J.;Li, B.;Chen, B.;Wang, J. R.;Liu, Y. B.;Yang, J. M.
已观察到miR-30d在人间变性甲状腺癌(ATC)中显著下调，并被认为是甲状腺细胞转化的重要事件。在这项研究中，我们发现miR-30d在调节ATC细胞对顺铂的敏感性方面发挥了关键作用，顺铂是治疗这种肿瘤的常用化疗药物。通过对miR-30d的模拟，我们证明miR-30d可以负向调节关键自噬基因beclin 1的表达，从而抑制顺铂激活的自噬反应，从而保护ATC细胞免于凋亡。报告基因分析表明，beclin 1-3‘非编码区中miR-30d的结合序列是该miRNA抑制beclin 1表达所必需的区域。我们进一步表明，在体外(细胞培养)和体内(动物异种移植模型)，miR-30d抑制Beclin 1介导的自噬可以模拟增敏的ATC细胞对顺铂的敏感性。这些结果表明，ATC细胞中miR-30d的失调是通过促进自噬存活而导致对顺铂不敏感的原因。因此，miR-30d有可能成为ATC治疗干预的潜在靶点。
miR-30d has been observed to be significantly down-regulated in human anaplastic thyroid carcinoma (ATC), and is believed to be an important event in thyroid cell transformation. In this study, we found that miR-30d has a critical role in modulating sensitivity of ATC cells to cisplatin, a commonly used chemotherapeutic drug for treatment of this neoplasm. Using a mimic of miR-30d, we demonstrated that miR-30d could negatively regulate the expression of beclin 1, a key autophagy gene, leading to suppression of the cisplatin-activated autophagic response that protects ATC cells from apoptosis. A reporter gene assay demonstrated that the binding sequences of miR-30d in the beclin 1-3′ UTR was the region required for the inhibition of beclin 1 expression by this miRNA. We further showed that inhibition of the beclin 1-mediated autophagy by the miR-30d mimic sensitized ATC cells to cisplatin both in vitro (cell culture) and in vivo (animal xenograft model). These results suggest that dysregulation of miR-30d in ATC cells is responsible for the insensitivity to cisplatin by promoting autophagic survival. Thus, miR-30d may be exploited as a potential target for therapeutic intervention in the treatment of ATC.
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影响因子：
5.8
作者：
Esposito, Francesco;Tornincasa, Mara;Fusco, Alfredo
通讯作者：
Fusco, Alfredo
影响因子：
8
作者：
Visone, R.;Pallante, P.;Fusco, A.
通讯作者：
Fusco, A.
影响因子：
13.3
作者：
Zhu, Hua;Wu, Hao;Yang, Jin-Ming
通讯作者：
Yang, Jin-Ming
影响因子：
8
作者：
Zhang, Y.;Cheng, Y.;Ren, X.;Zhang, L.;Yap, K. L.;Wu, H.;Patel, R.;Liu, D.;Qin, Z-H;Shih, I-M;Yang, J-M
通讯作者：
Yang, J-M
影响因子：
5.3
作者：
Harhaji-Trajkovic L;Vilimanovich U;Kravic-Stevovic T;Bumbasirevic V;Trajkovic V
通讯作者：
Trajkovic V