Department of Dermatology, The Affiliated Hospital of Guiyang Medical University, Yunyan, Guiyang, Guizhou 550004, P.R. China.
Oncol Rep. 2017 Aug;38(2):1276-1286. doi: 10.3892/or.2017.5740. Epub 2017 Jun 22.
MicroRNAs (miRNAs) play crucial roles in the initiation and progression of various cancers, including melanoma. Recently, the genetic variants and deregulation of miR-605 have been reported to participate in carcinogenesis. However, the expression status of the miR-605 in melanoma tissues and its role in melanoma progression remain unknown. In this study, we found that miR-605 was significantly downregulated in melanoma cell lines and clinical specimens. Further function studies demonstrated that miR-605 suppressed melanoma cell growth both in vitro and in vivo. Moreover, INPP4B gene was identified as a target of miR-605 through bioinformatics analysis and luciferase reporter assays. Further analysis demonstrated that the inhibition of INPP4B mediated SGK3 activation was required for the suppressive role of miR-605 on melanomas cell growth. Collectively, our data suggest that miR-605 functions as a tumor suppressor by negatively regulating INPP4B mediated SGK3 activation in melanoma and may present a potential target for therapeutic intervention.
微小 RNA（miRNA）在各种癌症的发生和发展中起着至关重要的作用，包括黑色素瘤。最近，miR-605 的遗传变异和失调被报道参与了癌变。然而，miR-605 在黑色素瘤组织中的表达状态及其在黑色素瘤进展中的作用尚不清楚。在本研究中，我们发现 miR-605 在黑色素瘤细胞系和临床标本中显著下调。进一步的功能研究表明，miR-605 抑制黑色素瘤细胞在体外和体内的生长。此外，通过生物信息学分析和荧光素酶报告基因实验，确定 INPP4B 基因为 miR-605 的靶基因。进一步的分析表明，抑制 INPP4B 介导的 SGK3 激活是 miR-605 抑制黑色素瘤细胞生长的必需条件。总之，我们的数据表明，miR-605 通过负调控 INPP4B 介导的 SGK3 激活在黑色素瘤中发挥肿瘤抑制作用，可能为治疗干预提供一个潜在的靶点。
