Department of Clinical Laboratory, Mianyang Central Hospital, Mianyang, China.
College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
J Cell Mol Med. 2020 Sep;24(17):9712-9725. doi: 10.1111/jcmm.15529. Epub 2020 Jul 30.
Renal cell carcinoma (RCC) is a common urologic malignancy, and up to 30% of RCC patients present with locally advanced or metastatic disease at the time of initial diagnosis. Increasing evidence suggests that circular RNAs (circRNAs) serve as genomic regulatory molecules in various human cancers. Our initial in silico microarray-based analysis identified that circRNA circ_001842 was highly expressed in RCC. Such up-regulation of circ_001842 in RCC was experimentally validated in tissues and cell lines using RT-qPCR. Thereafter, we attempted to identify the role of circ_001842 in the pathogenesis of RCC. Through a series of gain- and loss-of function assays, cell biological functions were examined using colony formation assay, Transwell assay, annexin V-FITC/PI-labelled flow cytometry and scratch test. A high expression of circ_001842 in tissues was observed as associated with poor prognosis of RCC patients. circ_001842 was found to elevate SLC39A14 expression by binding to miR-502-5p, consequently resulting in augmented RCC cell proliferation, migration and invasion, as well as EMT in vitro and tumour growth in vivo. These observations imply the involvement of circ_001842 in RCC pathogenesis through a miR-502-5p-dependent SLC39A14 mechanism, suggesting circ_001842 is a potential target for RCC treatment.
肾细胞癌（RCC）是一种常见的泌尿系统恶性肿瘤，多达 30%的 RCC 患者在初始诊断时就已处于局部晚期或转移性疾病。越来越多的证据表明，环状 RNA（circRNA）在各种人类癌症中充当基因组调节分子。我们最初的基于芯片的计算机分析表明，circRNA circ_001842 在 RCC 中表达水平较高。使用 RT-qPCR 在组织和细胞系中实验验证了 circ_001842 在 RCC 中的这种上调。此后，我们试图确定 circ_001842 在 RCC 发病机制中的作用。通过一系列的增益和功能丧失实验，使用集落形成实验、Transwell 实验、膜联蛋白 V-FITC/PI 标记的流式细胞术和划痕实验来检查细胞生物学功能。观察到 circ_001842 在组织中的高表达与 RCC 患者的预后不良相关。circ_001842 通过与 miR-502-5p 结合来上调 SLC39A14 的表达，从而导致体外 RCC 细胞增殖、迁移和侵袭以及 EMT 以及体内肿瘤生长增强。这些观察结果表明，circ_001842 通过依赖 miR-502-5p 的 SLC39A14 机制参与 RCC 的发病机制，表明 circ_001842 是 RCC 治疗的潜在靶点。
