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Circular RNA circ_001842 plays an oncogenic role in renal cell carcinoma by disrupting microRNA-502-5p-mediated inhibition of SLC39A14.
Journal of Cellular and Molecular Medicine ( IF 5.3 ) Pub Date : 2020-07-30 , DOI: 10.1111/jcmm.15529
Jiawei Zeng 1 , Qian Feng 2 , Yaodong Wang 3 , Gang Xie 4 , Yuanmeng Li 5 , Yuwei Yang 1 , Jiafu Feng 1, 5
Affiliation  

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.

中文翻译:

环状RNA circ_001842通过破坏microRNA-502-5p介导的SLC39A14抑制作用在肾细胞癌中发挥致癌作用。

肾细胞癌(RCC)是常见的泌尿系恶性肿瘤,在初次诊断时,多达30%的RCC患者出现局部晚期或转移性疾病。越来越多的证据表明,环状RNA(circRNA)在各种人类癌症中起着基因组调控分子的作用。我们最初的基于计算机芯片的计算机分析表明,circRNA circ_001842在RCC中高度表达。使用RT-qPCR在组织和细胞系中通过实验验证了RCC中circ_001842的这种上调。此后,我们试图确定circ_001842在RCC发病机理中的作用。通过一系列的功能获得和丧失功能测定,使用菌落形成测定,Transwell测定,膜联蛋白V‐FITC / PI标记的流式细胞仪和刮擦试验对细胞生物学功能进行了检查。观察到组织中circ_001842的高表达与RCC患者的预后不良有关。发现circ_001842通过与miR-502-5p结合来提高SLC39A14的表达,从而导致增强的RCC细胞增殖,迁移和侵袭,以及体外EMT和体内肿瘤生长。这些观察结果暗示circ_001842通过依赖miR-502-5p的SLC39A14机制参与RCC发病机制,表明circ_001842是RCC治疗的潜在靶标。
更新日期:2020-09-28
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