微小RNA-1246通过靶向叉头框蛋白A2促进黑色素瘤进展。
MicroRNA-1246 Promotes Melanoma Progression Through Targeting FOXA2.
作者信息
Yu Yanhua, Yu Fang, Sun Pijiang
机构信息
Department of Dermatology, Weihai Central Hospital Affiliated to Qingdao University, Weihai 264400, People's Republic of China.
Department of Hepatobiliary and Abdominal Hernias Surgery, Weihai Central Hospital Affiliated to Qingdao University, Weihai 264400, People's Republic of China.
出版信息
Onco Targets Ther. 2020 Feb 11;13:1245-1253. doi: 10.2147/OTT.S234276. eCollection 2020.
INTRODUCTION
Recently, the incidence of melanoma has been rising and there is a lack of effective targeted therapies. The regulatory mechanisms of microRNA-1246 (miR-1246) have been found in many cancers, except melanoma. This study focused on the regulatory mechanism of miR-1246 in melanoma development.
METHODS
The expression of miR-1246 was assessed using quantitative real-time polymerase chain reaction (RT-qPCR). Cell viability and metastasis were detected by Transwell and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays. The protein expression of epithelial mesenchymal transition (EMT) makers was assessed by Western blot analysis. The target gene of miR-1246 was detected using luciferase reporter assay.
RESULTS
MiR-1246 expression was increased in melanoma tissues and cells. In addition, upregulation of miR-1246 promoted cell viability and metastasis in melanoma. Forkhead box protein A2 (FOXA2) was confirmed to be a direct target of miR-1246. And FOXA2 expression was decreased in melanoma and was suppressed by miR-1246. Importantly, upregulation of FOXA2 restored the carcinogenesis of miR-1246 in melanoma.
CONCLUSION
MiR-1246 promoted cell viability and metastasis in melanoma by inhibiting FOXA2 expression.
引言
近年来，黑色素瘤的发病率一直在上升，且缺乏有效的靶向治疗方法。除黑色素瘤外，在许多癌症中都发现了微小RNA-1246（miR-1246）的调控机制。本研究聚焦于miR-1246在黑色素瘤发生发展中的调控机制。
方法
采用定量实时聚合酶链反应（RT-qPCR）评估miR-1246的表达。通过Transwell和MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）实验检测细胞活力和转移情况。通过蛋白质印迹分析评估上皮-间质转化（EMT）标志物的蛋白质表达。使用荧光素酶报告基因检测法检测miR-1246的靶基因。
结果
miR-1246在黑色素瘤组织和细胞中的表达增加。此外，miR-1246的上调促进了黑色素瘤细胞的活力和转移。叉头框蛋白A2（FOXA2）被证实是miR-1246的直接靶标。FOXA2在黑色素瘤中的表达降低，并受到miR-1246的抑制。重要的是，FOXA2的上调恢复了miR-1246在黑色素瘤中的致癌作用。
结论
miR-1246通过抑制FOXA2的表达促进黑色素瘤细胞的活力和转移。
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