期刊
CANCER LETTERS
卷 395, 期 -, 页码 53-62出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2017.02.033
关键词
microRNAs; Prostate cancer; Radiosensitivity; EMT; EGFR
类别
资金
- I. Monzino Foundation
- Italian Association for Cancer Research (AIRC) [ED12162]
- AIRC [MFAG11542, IG15191]
- AIRC fellowship [16360]
Radiotherapy is one of the main treatment choices for non-metastatic prostate cancer (PCa), although development of radioresistance limits its effectiveness. Mounting evidence supports the ability of microRNAs to interfere with different radioresistance-associated pathways, suggesting their potential as radiosensitizers. Here, we demonstrate that reconstitution of miR-875-5p, whose expression is down regulated in PCa clinical samples and directly correlates with that of E-cadherin, was able to enhance radiation response in PCa cell lines and xenografts through EGFR direct targeting. Consistent with the established role of EGFR in sustaining epithelial-to-mesenchymal transition (EMT) and promoting DNA repair following radiation-induced nuclear translocation, we found that miR-875-5p reconstitution in PCa cells counteracted EMT and impaired DNA lesion clearance. Down-regulation of the EMT-inducing transcription factor ZEB1, which also plays a role in homologous recombination-mediated repair of DNA lesions by regulating CHK1 expression, was found to be a major determinant of miR-875-5p-induced radiosensitization, as confirmed by phenocopy experiments showing that siRNA-mediated ZEB1 knockdown was able to reproduce the microRNA radiosensitizing effect. Overall, our data support the clinical interest in developing a novel therapeutic approach based on miR-875-5p reconstitution to increase PCa response to radiotherapy. (C) 2017 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据