Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Cancer Sci. 2021 Apr;112(4):1443-1456. doi: 10.1111/cas.14814. Epub 2021 Feb 10.
Emerging evidence revealed that circular RNAs (circRNAs) play significant roles in regulating tumorigenesis and cancer progression. However, few circRNAs were well characterized in clear cell renal cell carcinoma (ccRCC). We found that circPVT1 was significantly upregulated in ccRCC tissues and positively associated with the clinical stage. The Area Under Curve of tissue and serum circPVT1 expression in ccRCC were 0.93 and 0.86, respectively. Importantly, we demonstrated that circPVT1 promoted ccRCC growth and metastasis in vitro and in vivo. We also found that circPVT1 directly binds to miRNA-145-5p via the Biotin-labelled miRNA pulldown assay and dual-luciferase reporter assay, and miR-145-5p inhibitor significantly attenuated the effect of circPVT1 knockdown on ccRCC cells. Moreover, through RNA sequencing and bioinformatics analysis, we demonstrated that TBX15 was regulated by the circPVT1/miR-145-5p axis and predicted poor prognosis in ccRCC. These findings suggest that circPVT1 promotes ccRCC growth and metastasis through sponging miR-145-5p and regulating downstream target TBX15 expression. The circPVT1/miR-145-5p/TBX15 axis might be a potential diagnostic marker and therapeutic target in ccRCC.
新出现的证据表明,环状 RNA(circRNAs)在调节肿瘤发生和癌症进展方面发挥着重要作用。然而,在透明细胞肾细胞癌(ccRCC)中,很少有 circRNAs 得到很好的描述。我们发现 circPVT1 在 ccRCC 组织中显著上调,并与临床分期呈正相关。组织和血清 circPVT1 在 ccRCC 中的曲线下面积分别为 0.93 和 0.86。重要的是,我们证明了 circPVT1 在体外和体内促进了 ccRCC 的生长和转移。我们还发现 circPVT1 通过生物素标记的 miRNA 下拉测定和双荧光素酶报告基因测定直接与 miRNA-145-5p 结合,并且 miR-145-5p 抑制剂显著减弱了 circPVT1 敲低对 ccRCC 细胞的影响。此外,通过 RNA 测序和生物信息学分析,我们证明了 TBX15 受 circPVT1/miR-145-5p 轴的调节,并预测了 ccRCC 的不良预后。这些发现表明,circPVT1 通过海绵吸附 miR-145-5p 并调节下游靶标 TBX15 的表达来促进 ccRCC 的生长和转移。circPVT1/miR-145-5p/TBX15 轴可能是 ccRCC 的潜在诊断标志物和治疗靶点。