Mirzaei Hamed, Gholamin Sharareh, Shahidsales Soodabeh, Sahebkar Amirhossein, Jaafari Mahmoud Reza, Mirzaei Hamid Reza, Hassanian Seyed Mahdi, Avan Amir
Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Eur J Cancer. 2016 Jan;53:25-32. doi: 10.1016/j.ejca.2015.10.009. Epub 2015 Dec 13.
Melanoma is a life-threatening malignancy with poor prognosis and a relatively high burden of mortality in advanced stages. The efficacy of current available therapeutic strategies is limited, with a survival rate of less than 10%. Despite rapid advances in biomarker-guided drug development in different tumour types, including melanoma, only a very small number of biomarkers have been identified. Recently, microRNAs (miRNAs) have emerged as a molecular regulator in the development and progression of melanoma. Aberrant activation of some known miRNAs, e.g. let-7a and b, miR-148, miR-155, miR-182, miR-200c, miR-211, miR-214, miR-221 and 222, has been recognised to be linked with melanoma-associated genes such as NRAS, microphthalmia-associated transcription factor, receptor tyrosine kinase c-KIT, AP-2 transcription factor, etc. There is accumulating evidence suggesting the potential impact of circulating miRNAs as diagnostic and therapeutic markers in diseases. In addition, miRNAs have turned out to play important roles in drug-resistance mechanisms; suggesting their modulation as a potential approach to overcome chemoresistance. This review highlights recent preclinical and clinical studies on circulating miRNAs and their potential role as diagnosis, and therapeutic targets in melanoma.
黑色素瘤是一种危及生命的恶性肿瘤,预后较差,晚期死亡率负担相对较高。目前可用的治疗策略疗效有限,生存率低于10%。尽管在包括黑色素瘤在内的不同肿瘤类型中,生物标志物导向的药物开发取得了快速进展,但仅鉴定出极少数生物标志物。最近,微小RNA(miRNA)已成为黑色素瘤发生和发展过程中的一种分子调节因子。一些已知miRNA的异常激活,如let-7a和b、miR-148、miR-155、miR-182、miR-200c、miR-211、miR-214、miR-221和222,已被认为与NRAS、小眼相关转录因子、受体酪氨酸激酶c-KIT、AP-2转录因子等黑色素瘤相关基因有关。越来越多的证据表明,循环miRNA作为疾病诊断和治疗标志物具有潜在影响。此外,miRNA已被证明在耐药机制中发挥重要作用;这表明对其进行调节是克服化疗耐药性的一种潜在方法。本综述重点介绍了最近关于循环miRNA及其作为黑色素瘤诊断和治疗靶点的潜在作用的临床前和临床研究。