Cheng Yanfeng, Shen Peng
Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China.
Front Oncol. 2020 Mar 11;10:278. doi: 10.3389/fonc.2020.00278. eCollection 2020.
Recent development of integrative therapy against melanoma combines surgery, radiotherapy, targeted therapy, and immunotherapy; however, the clinical outcomes of advanced stage and recurrent melanoma are poor. As a skin cancer, melanoma is generally resistant to radiotherapy. Hence, there is an urgent need for evaluation of the mechanisms of radioresistance. The present study identified miR-335 as one of the differential expression of miRNAs in recurrent melanoma biopsies post-radiotherapy. The expression of miR-335 declined in melanoma tissues compared to the adjacent tissues. Moreover, miR-335 expression correlated with advanced stages of melanoma negatively. Consistent with the prediction of STARBASE and miRDB database, miR-335 targeted ROCK1 via binding with 3'-UTR of ROCK1 directly, resulting in attenuation of proliferation, migration, and radioresistance of melanoma cells. The authors validated that overexpression of miR-335 enhanced X-ray-induced tumor regression by B16 mouse models. Briefly, the present findings gained insights into miR-335/ROCK1-mediated radiosensitivity and provided a promising therapeutic strategy for improving radiotherapy against melanoma.
黑色素瘤综合治疗的最新进展包括手术、放疗、靶向治疗和免疫治疗；然而，晚期和复发性黑色素瘤的临床疗效较差。作为一种皮肤癌，黑色素瘤通常对放疗耐药。因此，迫切需要评估放疗抵抗的机制。本研究确定miR-335是放疗后复发性黑色素瘤活检组织中差异表达的miRNA之一。与相邻组织相比，黑色素瘤组织中miR-335的表达下降。此外，miR-335的表达与黑色素瘤的晚期阶段呈负相关。与STARBASE和miRDB数据库的预测一致，miR-335通过直接与ROCK1的3'-UTR结合靶向ROCK1，导致黑色素瘤细胞的增殖、迁移和放疗抵抗减弱。作者通过B16小鼠模型验证了miR-335的过表达增强了X射线诱导的肿瘤消退。简而言之，本研究结果深入了解了miR-335/ROCK1介导的放射敏感性，并为改善黑色素瘤放疗提供了一种有前景的治疗策略。
