Suppression of EIF4G2 by miR-379 potentiates the cisplatin chemosensitivity in nonsmall cell lung cancer cells
Suppression of EIF4G2 by miR-379 potentiates the cisplatin chemosensitivity in nonsmall cell lung cancer cells
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DOI：
10.1002/1873-3468.12566
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发表时间：
2017-02-01
期刊：
影响因子：
3.5
通讯作者：
Zhang, Bing-bing
中科院分区：
文献类型：
--
作者：
Hao, Guang-jun;Hao, Hai-jun;Zhang, Bing-bing
尽管已知microRNA和EIF 4G 2在癌症进展中发挥关键作用，但这些途径是否以协调的方式调节化学敏感性仍不清楚。在这里，我们发现miR-379的表达在化疗耐药的非小细胞肺癌（NSCLC）组织和细胞中显著下调。调控miR-379水平可以改变肺癌细胞（LCa）的体外和体内顺铂（CDDP）耐药性。在机制上，miR-379通过直接靶向EIF 4G 2 3UTR调节CDDP诱导的细胞凋亡来增强LCa化学敏感性。此外，我们观察到miR-379和EIF 4G 2表达之间的负相关性在LCa组织从患者的CDDP为基础的化疗。总之，我们的发现揭示了miR-379/EIF 4G 2级联在LCa中CDDP抗性发病机制中的潜在参与。
Although microRNAs and EIF4G2 are both known to play pivotal roles in cancer progression, it remains unknown whether these pathways regulate chemosensitivity in a coordinated manner. Here, we show that miR-379 expression is significantly downregulated in chemoresistant nonsmall cell lung cancer (NSCLC) tissues and cells. Manipulation of miR-379 levels could alter the in vitro and in vivo cisplatin (CDDP) resistance in lung cancer (LCa) cells. Mechanistically, miR-379 potentiated LCa chemosensitivity via modulation of CDDP-induced apoptosis by directly targeting the EIF4G2 3UTR. Additionally, we observed an inverse correlation between miR-379 and EIF4G2 expression in LCa tissues from patients with CDDP-based chemotherapy. Together, our findings shed new light on the potential involvement of miR-379/EIF4G2 cascade in the pathogenesis of CDDP resistance in LCa.