Chen Yonghui, Zhou Jiale, Wu Xiaorong, Huang Jiwei, Chen Wei, Liu Dongming, Zhang Jin, Huang Yiran, Xue Wei
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Transl Androl Urol. 2020 Apr;9(2):646-653. doi: 10.21037/tau.2019.12.10.
Yonghui Chen; Wei Xue. Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China. Email: cyh1488@163.com; xuewei@renji.com.
Aberrantly expressed microRNAs play important biological functions in the pathogenesis, progression and metastasis of numerous malignancies. Thus, further identification of these non-coding transcriptions is warranted.
miRNAs expression data of renal cell carcinoma (RCC) as well as the normal renal tissue samples was downloaded from TCGA and GEO database, and was analyzed by both computational and experimental approaches. The bio-functional role of the miRNA was then moreover identified by over-expression and inhibition assays. Beyond that, Western blots, luciferase assays, along with immunohistochemistry (IHC) tests were conducted for further study of the potential mechanisms.
In this study, a novel regulatory miRNA, miR-30a-3p, was identified along with its biological function as well as prognostic value in RCC. Functionally, miR-30a-3p inhibits RCC cell invasion and migration. miR-30a-3p targets autophagy related 12 (ATG12), which we confirmed by luciferase reporter assays and Western blotting.
In conclusion, miR-30a-3p, as a new prognostic marker in RCC, down-regulates RCC cell invasion and migration by targeting ATG12. This consistently improves the overall survival of RCC patients.
陈永辉;薛巍。上海交通大学医学院附属仁济医院泌尿外科,上海200127,中国。电子邮箱:cyh1488@163.com;xuewei@renji.com。
异常表达的微小RNA在众多恶性肿瘤的发病机制、进展和转移中发挥重要生物学功能。因此,有必要进一步鉴定这些非编码转录物。
从TCGA和GEO数据库下载肾细胞癌(RCC)以及正常肾组织样本的微小RNA表达数据,并通过计算和实验方法进行分析。此外,通过过表达和抑制试验确定微小RNA的生物功能作用。除此之外,进行蛋白质免疫印迹、荧光素酶测定以及免疫组织化学(IHC)检测以进一步研究潜在机制。
在本研究中,鉴定出一种新型调控微小RNA,即miR-30a-3p,及其在RCC中的生物学功能和预后价值。在功能上,miR-30a-3p抑制RCC细胞侵袭和迁移。miR-30a-3p靶向自噬相关蛋白12(ATG12),这通过荧光素酶报告基因测定和蛋白质免疫印迹得以证实。
总之,miR-30a-3p作为RCC中的一种新的预后标志物,通过靶向ATG12下调RCC细胞侵袭和迁移。这持续改善RCC患者的总生存期。