Ye Zhiqiang, Yin Shengli, Su Zhongzhen, Bai Mingjun, Zhang Haibo, Hei Ziqing, Cai Songwang
Department of Emergency, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Oncotarget. 2016 Jun 21;7(25):37524-37535. doi: 10.18632/oncotarget.6852.
Chemoresistance and epithelial-mesenchymal transition (EMT) in cancer are linked phenomena. EMT contributes to chemoresistance, however, little is known about whether chemotherapy can induce EMT in cancer cells. Here, we found that miR-101 expression was downregulated in cisplatin-resistant non-small cell lung cancer (NSCLC) cells. Restoration of miR-101 expression inhibited EMT and increased the sensitivity of cisplatin-resistant NSCLC cells to cisplatin in vitro by targeting ROCK2. Furthermore, ROCK2 protein level was inversely correlated with miR-101 level in NSCLC tissue samples. Kaplan-Meier analysis revealed that low miR-101 expression in NSCLC was correlated with poor survival time. In summary, our results provide novel mechanistic insights into the role of miR-101/ROCK2 signaling in the cisplatin resistance of NSCLC cells. Targeting of miR-101 is a potential therapeutic approach for NSCLC.
癌症中的化疗耐药性与上皮-间质转化（EMT）是相关联的现象。EMT会导致化疗耐药，然而，关于化疗是否能诱导癌细胞发生EMT却知之甚少。在此，我们发现miR-101在顺铂耐药的非小细胞肺癌（NSCLC）细胞中表达下调。通过靶向ROCK2，恢复miR-101的表达可在体外抑制EMT并增加顺铂耐药NSCLC细胞对顺铂的敏感性。此外，在NSCLC组织样本中，ROCK2蛋白水平与miR-101水平呈负相关。Kaplan-Meier分析显示，NSCLC中miR-101低表达与较差的生存时间相关。总之，我们的结果为miR-101/ROCK2信号通路在NSCLC细胞顺铂耐药中的作用提供了新的机制性见解。靶向miR-101是NSCLC的一种潜在治疗方法。
