a Department of Urology Surgery , The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology , Luoyang , China.
Cell Cycle. 2018;17(23):2644-2654. doi: 10.1080/15384101.2018.1553354. Epub 2018 Dec 10.
Increasing evidence showed that circular RNAs (circRNAs) play critical roles in tumorigenesis. However, the roles and underlying mechanisms of circRNAs in clear cell renal cell carcinoma (ccRCC) remain unclear. In the present study, we identified a novel circRNA circPCNXL2, which was significantly upregulated in ccRCC by circular RNA microarray. Further analysis revealed that circPCNXL2 was significantly increased and correlated with poor overall survival of ccRCC patients. Function assays revealed that circPCNXL2 knockdown reduced RCC cells proliferation, invasion in vitro, and decreased tumor growth in vivo. In mechanism study, we showed that circPCNXL2 could be bind to miR-153 as a miRNA sponge to regulate ZEB2 expression in RCC progression. In addition, our data reported that the effects of circPCNXL2 inhibition on RCC cells proliferation and invasion could be abolished by miR-153 inhibitors. Altogether, we demonstrated that circPCNXL2 could regulate RCC cells proliferation and invasion by miR-153/ZEB2 axis, suggesting circPCNXL2 might serve as a potential therapeutic target for ccRCC treatment.
越来越多的证据表明,环状 RNA(circRNAs)在肿瘤发生中发挥着关键作用。然而,circRNAs 在透明细胞肾细胞癌(ccRCC)中的作用及其潜在机制尚不清楚。在本研究中,我们通过环状 RNA 微阵列鉴定了一种新型的 circRNA circPCNXL2,它在 ccRCC 中显著上调。进一步分析表明,circPCNXL2 显著增加,并与 ccRCC 患者的总体生存不良相关。功能分析表明,circPCNXL2 的敲低可减少体外 RCC 细胞的增殖和侵袭,并降低体内肿瘤生长。在机制研究中,我们表明 circPCNXL2 可以作为 miRNA 海绵与 miR-153 结合,从而调节 RCC 进展中的 ZEB2 表达。此外,我们的数据表明,circPCNXL2 抑制对 RCC 细胞增殖和侵袭的影响可以被 miR-153 抑制剂消除。综上所述,我们证明 circPCNXL2 可以通过 miR-153/ZEB2 轴调节 RCC 细胞的增殖和侵袭,表明 circPCNXL2 可能作为 ccRCC 治疗的潜在治疗靶点。