Guan Yongjun, Gong Zhimin, Xiao Tianlin, Li Zhaoyuan
Department of Urology Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science 441021, China.
Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science 441021, China.
Int J Clin Exp Pathol. 2018 Dec 1;11(12):5705-5714. eCollection 2018.
Renal cell carcinoma (RCC) is one of the most common types of cancer. miR-572 has been proposed to be implicated in a number of human cancers, including RCC. Nevertheless, the detailed functions and molecular mechanisms of miR-572 in RCC have not been well illustrated. qRT-PCR assay was used to assess the expression of miR-572 in RCC specimens and cell lines. Loss-of-function experiments were carried out to explore the effect of miR-572 on proliferation and apoptosis in 786-O cells. Predicted by TargetScan, the interaction between miR-572 and neurofibromin 2 (NF2) was explored by dual-luciferase reporter assay and western blot analysis. To investigate whether the regulatory effect of miR-572 was mediated by NF2, 786-O cells were transfected with anti-miR-572 alone, or together with si-NF2. After that, western blot assay was used to validate whethermiR-572 regulated proliferation and apoptosis of the RCC cell line through NF2/Hippo signaling. miR-572 expression was upregulated in RCC specimens and cell lines, and miR-572 knockdown suppressed proliferation and enhanced apoptosis in 786-O cells. miR-572 repressed NF2 expression by binding to NF2 mRNA 3'-UTR. Moreover, the anti-miR-572-mediated regulatory effect on proliferation and apoptosis was abated by the restoration of NF2 expression in RCC cells. Furthermore, miR-572 knockdown activated NF2/Hippo signaling pathway in RCC cells. The regulatory effect of miR-572 on proliferation and apoptosis is mediated through modulating NF2/Hippo signaling in RCC cell lines, providing a novel potential strategy for RCC.
肾细胞癌（RCC）是最常见的癌症类型之一。miR - 572已被提出与包括RCC在内的多种人类癌症有关。然而，miR - 572在RCC中的详细功能和分子机制尚未得到充分阐明。采用qRT - PCR检测法评估miR - 572在RCC标本和细胞系中的表达。进行功能缺失实验以探究miR - 572对786 - O细胞增殖和凋亡的影响。通过TargetScan预测，采用双荧光素酶报告基因检测法和蛋白质免疫印迹分析探究miR - 572与神经纤维瘤蛋白2（NF2）之间的相互作用。为了研究miR - 572的调节作用是否由NF2介导，单独用抗miR - 572或与si - NF2一起转染786 - O细胞。之后，采用蛋白质免疫印迹检测法验证miR - 572是否通过NF2/河马信号通路调节RCC细胞系的增殖和凋亡。miR - 572在RCC标本和细胞系中表达上调，敲低miR - 572可抑制786 - O细胞的增殖并增强其凋亡。miR - 572通过与NF2 mRNA 3'-UTR结合抑制NF2表达。此外，在RCC细胞中恢复NF2表达可减弱抗miR - 572介导的对增殖和凋亡的调节作用。此外，敲低miR - 572可激活RCC细胞中的NF2/河马信号通路。miR - 572对增殖和凋亡的调节作用是通过调节RCC细胞系中的NF2/河马信号通路介导的，为RCC提供了一种新的潜在治疗策略。
