Peng Zheng, Xu Tiancai, Liao Xiaofang, He Huijuan, Xu Wansu
Department of Radiation Oncology, Quzhou People Hospital, Zhongloudi Road, Quzhou, 324000, China,
Tumour Biol. 2016 Dec;37:15559–15566. doi: 10.1007/s13277-015-3960-7. Epub 2015 Aug 29.
Radiotherapy is widely used in the treatment of nasopharyngeal carcinoma (NPC), whereas its effects on the NPC growth, survival, and metastases have not been completely evaluated. Here, we compared the detected metastatic NPC tissues after radiotherapy (m-NPC) to the resected primary NPC tissues prior to radiotherapy (p-NPC). We detected higher levels of Snail2 protein, but not mRNA in m-NPC, compared to p-NPC. In vitro, a modest irradiation on NPC cells resulted in significant cell death, but increased Snail2 protein, but mRNA levels in the surviving NPC cells. Bioinformatics analyses showed that miR-613, which was significantly decreased in NPC cells after irradiation, targeted the 3'-UTR of Snail2 mRNA to inhibit its translation. Moreover, miR-613 overexpression inhibited Snail2-mediated cell invasiveness, while miR-613 depletion increased Snail2-mediated cell invasiveness in NPC cells. Finally, we detected significantly lower levels of miR-613 in m-NPC, compared to p-NPC. Together our data suggest that although radiotherapy induced NPC cell death, it may increase Snail2-mediated NPC cell invasiveness through downregulating miR-613.
放射疗法广泛应用于鼻咽癌(NPC)的治疗,但其对NPC生长、存活和转移的影响尚未得到全面评估。在此,我们将放疗后检测到的转移性NPC组织(m-NPC)与放疗前切除的原发性NPC组织(p-NPC)进行了比较。与p-NPC相比,我们在m-NPC中检测到更高水平的Snail2蛋白,但未检测到mRNA水平升高。在体外,对NPC细胞进行适度照射会导致显著的细胞死亡,但会增加存活NPC细胞中Snail2蛋白和mRNA水平。生物信息学分析表明,照射后NPC细胞中显著降低的miR-613靶向Snail2 mRNA的3'-UTR以抑制其翻译。此外,miR-613过表达抑制Snail2介导的细胞侵袭,而miR-613缺失则增加NPC细胞中Snail2介导的细胞侵袭。最后,与p-NPC相比,我们在m-NPC中检测到显著更低水平的miR-613。我们的数据共同表明,尽管放疗诱导NPC细胞死亡,但它可能通过下调miR-613增加Snail2介导的NPC细胞侵袭。