Chen Zhenhua, Zhang Jiaxing, Zhang Zhiling, Feng Zihao, Wei Jinhuan, Lu Jun, Fang Yong, Liang Yanping, Cen Junjie, Pan Yihui, Huang Yong, Zhou Fangjian, Chen Wei, Luo Junhang
Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Cell Death Dis. 2017 Jun 1;8(6):e2859. doi: 10.1038/cddis.2017.252.
Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma, can easily invade local tissues and metastasize, and is resistant to currently available treatments. Recent studies profiling microRNA expression in ccRCC have suggested miR-30a-5p may be deregulated in these cancer cells. To determine its role and mechanism of action in ccRCC, miR-30-5p expression levels were quantified and functions were analyzed using in vitro and in vivo experiments and bioinformatics. A decrease in miR-30a-5p expression was frequently noted in ccRCC cells and tissues. Importantly, low miR-30a-5p levels were significantly associated with a poor ccRCC patient prognosis. Stable overexpression of miR-30a-5p in 769-P cells was sufficient to prevent cellular proliferation and invasion in vitro and in vivo. Upon further examination, it was found that miR-30a-5p directly targeted the 3'-UTR of ZEB2 and suppressed ccRCC cell epithelial-mesenchymal transition. In addition, miR-30a-5p may be downregulated by the long non-coding RNA DLEU2. Taken together, these data reveal an important role for miR-30a-5p in the regulation of ccRCC proliferation and invasion, and indicate the potential for miR-30a-5p in applications furthering ccRCC prognostics and therapeutics.
透明细胞肾细胞癌(ccRCC)是肾细胞癌最常见的亚型,极易侵犯局部组织并发生转移,且对目前可用的治疗方法具有抗性。最近对ccRCC中微小RNA表达进行分析的研究表明,miR-30a-5p在这些癌细胞中可能表达失调。为了确定其在ccRCC中的作用和作用机制,通过体外和体内实验以及生物信息学对miR-30-5p的表达水平进行了定量分析,并对其功能进行了分析。在ccRCC细胞和组织中经常发现miR-30a-5p表达降低。重要的是,低水平的miR-30a-5p与ccRCC患者的不良预后显著相关。在769-P细胞中稳定过表达miR-30a-5p足以在体外和体内抑制细胞增殖和侵袭。进一步研究发现,miR-30a-5p直接靶向ZEB2的3'-UTR并抑制ccRCC细胞的上皮-间质转化。此外,miR-30a-5p可能被长链非编码RNA DLEU2下调。综上所述,这些数据揭示了miR-30a-5p在调节ccRCC增殖和侵袭中的重要作用,并表明miR-30a-5p在改善ccRCC预后和治疗方面的应用潜力