Luan Wenkang, Qian Yao, Ni Xin, Bu Xuefeng, Xia Yun, Wang Jinlong, Ruan Hongru, Ma Shaojun, Xu Bin
Department of Plastic Surgery.
Department of Neurosurgery.
Onco Targets Ther. 2017 Feb 27;10:1237-1246. doi: 10.2147/OTT.S128819. eCollection 2017.
An increasing number of microRNAs have been found to be involved in tumorigenesis, including melanoma tumorigenesis. miR-204-5p is down-regulated and functions as a tumor suppressor in many human malignant tumors. miR-204-5p expression is also decreased in melanoma tissues, but its biological roles and molecular mechanisms in malignant melanoma remain unclear. In this study, the aberrant down-regulation of miR-204-5p was detected in melanoma, especially in metastatic melanoma. miR-204-5p also served as a protective factor for the prognosis of melanoma patients. We determined that miR-204-5p suppresses cell proliferation, migration and invasion, and promotes cell apoptosis in melanoma. Matrix metalloproteinases-9 and B-cell lymphoma-2 are the functional targets of miR-204-5p, through which it plays an important biological role in malignant melanoma. The effect of miR-204-5p on malignant melanoma is verified using a xenograft model. We also determined that miR-204-5p increases 5-fluorouracil and cisplatin (DDP) chemosensitivity in malignant melanoma cells. This finding elucidates new functions and mechanisms for miR-204-5p in melanoma development, and provides potential therapeutic targets for the treatment of melanoma.
越来越多的微小RNA被发现参与肿瘤发生，包括黑色素瘤的肿瘤发生。miR-204-5p在许多人类恶性肿瘤中表达下调并发挥肿瘤抑制作用。黑色素瘤组织中miR-204-5p的表达也降低，但其在恶性黑色素瘤中的生物学作用和分子机制仍不清楚。在本研究中，在黑色素瘤中检测到miR-204-5p异常下调，尤其是在转移性黑色素瘤中。miR-204-5p也是黑色素瘤患者预后的保护因素。我们确定miR-204-5p在黑色素瘤中抑制细胞增殖、迁移和侵袭，并促进细胞凋亡。基质金属蛋白酶-9和B细胞淋巴瘤-2是miR-204-5p的功能靶点，通过它们miR-204-5p在恶性黑色素瘤中发挥重要生物学作用。使用异种移植模型验证了miR-204-5p对恶性黑色素瘤的作用。我们还确定miR-204-5p增加恶性黑色素瘤细胞对5-氟尿嘧啶和顺铂（DDP）的化疗敏感性。这一发现阐明了miR-204-5p在黑色素瘤发展中的新功能和机制，并为黑色素瘤的治疗提供了潜在的治疗靶点。
