Hao Guang-Jun, Hao Hai-Jun, Ding Yan-Hui, Wen Hui, Li Xiao-Feng, Wang Qian-Ru, Zhang Bing-Bing
Department of Oncology, First Hospital of Yulin City, China.
Department of Clinical Laboratory, First Hospital of Yulin City, China.
FEBS Lett. 2017 Feb;591(4):636-645. doi: 10.1002/1873-3468.12566. Epub 2017 Feb 20.
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 3'UTR. 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.
尽管已知微小RNA和EIF4G2在癌症进展中都起着关键作用,但这些通路是否以协调的方式调节化疗敏感性仍不清楚。在这里,我们表明miR-379在化疗耐药的非小细胞肺癌(NSCLC)组织和细胞中表达显著下调。操纵miR-379水平可改变肺癌(LCa)细胞在体外和体内对顺铂(CDDP)的耐药性。从机制上讲,miR-379通过直接靶向EIF4G2的3'UTR调节CDDP诱导的细胞凋亡,从而增强LCa的化疗敏感性。此外,我们观察到在接受基于CDDP化疗的患者的LCa组织中,miR-379与EIF4G2表达呈负相关。总之,我们的研究结果为miR-379/EIF4G2级联在LCa中CDDP耐药发病机制中的潜在作用提供了新的线索。