Shao Qianqian, Zhang Pei, Ma Yingye, Lu Zhaoyi, Meng Jie, Li Hui, Wang Xiaoming, Chen Deshang, Zhang Mingjie, Han Yaofeng, Liu Hao, Ma Shiyin
Department of Otolaryngology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China.
Faculty of Pharmacy, Bengbu Medical College, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, Anhui 233030, China.
Gene. 2018 Apr 30;652:48-58. doi: 10.1016/j.gene.2018.02.003. Epub 2018 Feb 8.
Nasopharyngeal carcinoma (NPC) is a head and neck cancer associated with poor prognosis. Many studies have shown that the epithelial-to-mesenchymal transition (EMT) is important in cancer progression, metastasis, and chemotherapy resistance and that microRNAs (miRNAs) play a key role in chemotherapy resistance associated with EMT. The miRNA miR-139-5p is downregulated in many human cancers and is closely related to tumor progression. The aim of this study was to investigate the ability of miR-139-5p to influence the cisplatin resistance, apoptosis, invasion and migration in NPC cells through the regulation of the EMT. We investigated these processes in parental HNE1 and cisplatin-resistant HNE1/DDP cells transfected with miR-139-5p inhibitors and mimics, respectively. Our results suggest that the upregulation of miR-139-5p expression inhibits proliferation, invasion, migration and EMT in human NPC cells. In addition, we found that miR-139-5p expression levels and DDP-induced apoptosis positively correlate in NPC cells. In conclusion, our results demonstrate that miR-139-5p can regulate the migration, invasion and DDP resistance in human NPC by modulating the EMT. The regulation of miR-139-5p levels might be a new approach to reverse EMT and DDP resistance and counteract metastasis and chemotherapy resistance in human NPC.
鼻咽癌(NPC)是一种预后较差的头颈癌。许多研究表明,上皮-间质转化(EMT)在癌症进展、转移和化疗耐药中起重要作用,且微小RNA(miRNA)在与EMT相关的化疗耐药中起关键作用。miRNA miR-139-5p在许多人类癌症中表达下调,且与肿瘤进展密切相关。本研究的目的是通过调节EMT来研究miR-139-5p影响NPC细胞顺铂耐药、凋亡、侵袭和迁移的能力。我们分别用miR-139-5p抑制剂和模拟物转染亲本HNE1和顺铂耐药的HNE1/DDP细胞,研究了这些过程。我们的结果表明,miR-139-5p表达上调可抑制人NPC细胞的增殖、侵袭、迁移和EMT。此外,我们发现NPC细胞中miR-139-5p表达水平与顺铂诱导的凋亡呈正相关。总之,我们的结果表明,miR-139-5p可通过调节EMT来调控人NPC的迁移、侵袭和顺铂耐药。调节miR-139-5p水平可能是逆转EMT和顺铂耐药以及对抗人NPC转移和化疗耐药的一种新方法。