Zhu Xuchao, Li Dan, Yu Fei, Jia Chengyou, Xie Jing, Ma Yushui, Fan Suyun, Cai Haidong, Luo Qiong, Lv Zhongwei, Fan Lihong
Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China.
Department of Respiration, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China.
Oncotarget. 2016 Mar 15;7(11):13139-52. doi: 10.18632/oncotarget.7545.
Recent studies have implied that miRNAs may play a crucial role in tumor progression and may be involved in the modulation of some drug resistance in cancer cells. Earlier studies have demonstrated that miR-194 was involved in tumor metastasis and drug resistance in non-small cell lung cancer (NSCLC), whereas their expression and roles on NSCLC still need further elucidation. In the current study, we found that miR-194 is decreased in NSCLC samples compared with adjacent non-cancerous lung samples, and low expression of miR-194 predicts poor patient survival. Both in vitro and in vivo experiments showed that ectopic stable expression miR-194 suppressed proliferation, migration, invasion and metastasis and induced apoptosis in NSCLC cells and that this suppression could be reversed by reintroducing forkhead box A1 (FOXA1), a functional target of miR-194. In addition, miR-194 was downregulated in in cisplatin-resisted human NSCLC cell line-A549/DDP and overexpression of miR-194 increases cisplatin sensitivity. These findings suggested that miR-194 inhibits proliferation and metastasis and reverses cisplatin-resistance of NSCLC cells and may be useful as a new potential therapeutic target for NSCLC.
近期研究表明,微小RNA(miRNAs)可能在肿瘤进展中发挥关键作用,并且可能参与癌细胞某些耐药性的调节。早期研究已证明,miR-194参与非小细胞肺癌(NSCLC)的肿瘤转移和耐药,然而其在NSCLC中的表达及作用仍需进一步阐明。在本研究中,我们发现与相邻的非癌肺组织样本相比,NSCLC样本中miR-194表达降低,且miR-194低表达预示患者预后不良。体外和体内实验均表明,异位稳定表达miR-194可抑制NSCLC细胞的增殖、迁移、侵袭和转移,并诱导其凋亡,而重新引入miR-194的功能性靶标叉头框A1(FOXA1)可逆转这种抑制作用。此外,在顺铂耐药的人NSCLC细胞系A549/DDP中miR-194表达下调,过表达miR-194可增加顺铂敏感性。这些发现提示,miR-194可抑制NSCLC细胞的增殖和转移,并逆转其顺铂耐药性,可能作为NSCLC一种新的潜在治疗靶点。