Lu Ruijing, Ji Ziliang, Li Xiaoqing, Qin Jie, Cui Guanghui, Chen Jing, Zhai Qingna, Zhao Chunjuan, Zhang Wei, Yu Zhendong
Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
Clinical Laboratory, Bao'an District of Shenzhen Maternity and Child Health Hospital, Shenzhen, 518133, China.
Tumour Biol. 2015 Sep;36(9):6691-700. doi: 10.1007/s13277-015-3355-9. Epub 2015 Mar 27.
A large body of evidence indicates that microRNAs play a critical role in tumor initiation and progression by negatively regulating oncogenes or tumor suppressor genes. Here, we report that the expression of miR-200a was notably downregulated in 45 renal cell carcinoma (RCC) samples. Restoration of miR-200a suppressed cell proliferation, migration, and invasion in two RCC cell lines. Furthermore, we used an epithelial-to-mesenchymal transition PCR array to explore the putative target genes of miR-200a. By performing quantitative real-time PCR, ELISA, and luciferase reporter assays, transforming growth factor beta2 (TGFB2) was validated as a direct target gene of miR-200a. Moreover, siRNA-mediated knockdown of TGFB2 partially phenocopied the effect of miR-200a overexpression. These results suggest that miR-200a suppresses RCC development via directly targeting TGFB2, indicating that miR-200a may present a novel target for diagnostic and therapeutic strategies in RCC.
大量证据表明，微小RNA通过负调控癌基因或肿瘤抑制基因在肿瘤的起始和进展中发挥关键作用。在此，我们报告称，在45例肾细胞癌（RCC）样本中，miR-200a的表达显著下调。恢复miR-200a可抑制两种RCC细胞系的细胞增殖、迁移和侵袭。此外，我们使用上皮-间质转化PCR阵列来探索miR-200a的假定靶基因。通过进行定量实时PCR、ELISA和荧光素酶报告基因测定，转化生长因子β2（TGFB2）被验证为miR-200a的直接靶基因。此外，siRNA介导的TGFB2敲低部分模拟了miR-200a过表达的效果。这些结果表明，miR-200a通过直接靶向TGFB2抑制RCC的发展，这表明miR-200a可能为RCC的诊断和治疗策略提供一个新的靶点。
