Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Am J Pathol. 2019 Dec;189(12):2469-2486. doi: 10.1016/j.ajpath.2019.06.016. Epub 2019 Aug 30.
Many studies have recognized that circular RNAs (circRNAs) can be promising targets for renal cell carcinoma (RCC) by acting as competing endogenous RNAs for miRNAs. This study intends to uncover the implication of a novel circRNA, circ_000926 in RCC, and how it affects tumorigenesis. Microarray-based circRNA/gene expression profiling of RCC was used to identify differentially expressed circRNAs/genes in RCC and normal tissues. miRNAs targeting the screened circRNAs/genes were predicted online, followed by analyzing circ_000926 expression in RCC. The crosstalk among circ_000926, miRNA-411 (miR-411), and CDH2 was then validated. The expression of circ_000926, miR-411, and cadherin 2 (CDH2) was up-regulated or down-regulated in RCC cells to unearth their effects on the biological behaviors of RCC cells. circ_000926 was highly expressed in RCC tissues and cell lines, whereas CDH2 was verified to be a target of miR-411. As a competing endogenous RNA, circ_000926 could directly bind to miR-411 to up-regulate CDH2. Down-regulation of circ_000926 resulted in inhibited growth, migration, and invasion abilities of RCC cells, as well as suppressed epithelial-mesenchymal transition and tumor growth. However, the inhibition of miR-411 or elevation of CDH2 reversed the antitumor effects induced by silencing circ_000926. Down-regulation of circ_000926 exerts an inhibitory effect on RCC progression through miR-411-dependent CDH2 inhibition, highlighting a potential target for RCC treatment.
许多研究已经认识到，环状 RNA（circRNAs）可以通过作为 miRNA 的竞争性内源性 RNA 成为肾细胞癌（RCC）的有希望的靶点。本研究旨在揭示一种新型环状 RNA，circ_000926 在 RCC 中的作用及其对肿瘤发生的影响。使用基于微阵列的 RCC 环状 RNA/基因表达谱分析来鉴定 RCC 和正常组织中差异表达的环状 RNA/基因。在线预测靶向筛选出的环状 RNA/基因的 miRNA，然后分析 RCC 中 circ_000926 的表达。然后验证 circ_000926、miR-411（miR-411）和 CDH2 之间的串扰。上调或下调 RCC 细胞中的 circ_000926、miR-411 和钙粘蛋白 2（CDH2），以揭示它们对 RCC 细胞生物学行为的影响。circ_000926 在 RCC 组织和细胞系中高表达，而 CDH2 被验证为 miR-411 的靶标。作为竞争性内源性 RNA，circ_000926 可以直接与 miR-411 结合以上调 CDH2。下调 circ_000926 导致 RCC 细胞的生长、迁移和侵袭能力受到抑制，并抑制上皮-间充质转化和肿瘤生长。然而，抑制 miR-411 或上调 CDH2 逆转了沉默 circ_000926 诱导的抗肿瘤作用。下调 circ_000926 通过 miR-411 依赖性 CDH2 抑制对 RCC 进展发挥抑制作用，突出了 RCC 治疗的潜在靶点。
