Fang Wei, Fan Yibin, Fa Zhenzong, Xu Jinhua, Yu Hongyu, Li Pu, Gu Julin
Shanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology and Venereology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Oncotarget. 2017 Feb 21;8(8):13253-13263. doi: 10.18632/oncotarget.14710.
Dysregulated microRNA (miR)-625 expression has been observed in several kinds of cancer. MicroRNAs are important factors in the development and progression of malignant melanoma, though the clinical significance and function of miR-625 in human malignant melanoma remain unclear. Levels of miR-625 expression were therefore determined in 36 pairs of malignant melanoma and adjacent non-tumor tissue using qPCR. The effects of miR-625 dysregulation on malignant melanoma cell proliferation, wound healing, migration and invasion in vitro and tumorigenicity in vivo were investigated using CCK-8, transwell assays, and a nude mouse subcutaneous tumor model. Bioinformatics analysis and luciferase reporter system were used to predict and confirm the target gene of miR-625. miR-625 levels were frequently decreased in malignant melanoma. Ectopic expression of miR-625 suppressed proliferation, wound healing, migration, and tumorgenicity in malignant melanoma. Moreover, miR-625 acted, at least in part, by suppressing potential target SOX2. These results show that miR-625 is a tumor suppressor that inhibits the development and progression of malignant melanoma, which suggests miR-625 is potentially a new diagnostic marker and therapeutic target of malignant melanoma.
在几种癌症中均观察到微小RNA(miR)-625表达失调。微小RNA是恶性黑色素瘤发生和发展的重要因素,尽管miR-625在人类恶性黑色素瘤中的临床意义和功能仍不清楚。因此,使用qPCR检测了36对恶性黑色素瘤组织和相邻非肿瘤组织中miR-625的表达水平。利用CCK-8、transwell实验和裸鼠皮下肿瘤模型,研究了miR-625失调对恶性黑色素瘤细胞体外增殖、伤口愈合、迁移和侵袭以及体内致瘤性的影响。采用生物信息学分析和荧光素酶报告系统预测并验证miR-625的靶基因。恶性黑色素瘤中miR-625水平经常降低。miR-625的异位表达抑制了恶性黑色素瘤的增殖、伤口愈合、迁移和致瘤性。此外,miR-625至少部分通过抑制潜在靶标SOX2发挥作用。这些结果表明,miR-625是一种肿瘤抑制因子,可抑制恶性黑色素瘤的发生和发展,这表明miR-625可能是恶性黑色素瘤的一种新的诊断标志物和治疗靶点。