环状 RNA_001287 通过靶向 miR-144 调控 CEP55 促进肾细胞癌进展

Tumor promoting effects of circRNA_001287 on renal cell carcinoma through miR-144-targeted CEP55.

机构信息

Department of Clinical Laboratory, Mianyang Central Hospital, No. 12, Changjia Lane, Jingzhong Street, Fucheng District, Sichuan Province, 621000, Mianyang, PR China.

Clinical Laboratory of Traditional, Chinese Medicine Hospital Affiliated to Southwest Medical University, 646000, Luzhou, Province, PR China.

出版信息

J Exp Clin Cancer Res. 2020 Dec 1;39(1):269. doi: 10.1186/s13046-020-01744-2.

Abstract

BACKGROUND

Renal cell carcinoma (RCC) is a common urological cancer. circular RNAs (circRNAs) is involved in the development of various types of cancers. However, the roles and underlying mechanisms of circRNAs in RCC are not fully elucidated. Herein, we aimed to examine the potential effect of circ_001287 on RCC progression.

MATERIALS AND METHODS

Microarray-based gene expression profiling of RCC was initially employed in order to identify differentially expressed genes. Next, the expression of circ_001287 was examined, and the cell line with the highest circ_001287 expression was selected for subsequent investigation. The interaction among circ_001287, miR-144, and CEP55 was identified by conducting luciferase reporter assay, RNA-pull down, RIP, RT-qPCR and FISH. The effect of circ_001287 on proliferative, invasive and migratory capacities as well as tumorigenicity of transfected cells in mice was examined using gain- and loss-of-function experiments.

RESULTS

circ_001287 and CEP55 were highly expressed while miR-144 was decreased in RCC tissues and cell lines. circ_001287 can up-regulate CEP55 by binding to miR-144, which resulted in increased proliferative, invasive and migratory capacities and tumor growth in vivo. In addition, down-regulation of miR-144 was also observed to promote these biological activities.

CONCLUSIONS

Overall, these results elucidate a new mechanism for circ_001287 in RCC development and provide a potential therapeutic target for RCC patients.

摘要

背景

肾细胞癌(RCC)是一种常见的泌尿系统癌症。环状 RNA(circRNA)参与了多种类型癌症的发生发展。然而,circRNA 在 RCC 中的作用和潜在机制尚不完全清楚。在此,我们旨在研究 circ_001287 对 RCC 进展的潜在影响。

材料与方法

首先采用基于微阵列的基因表达谱分析 RCC,以鉴定差异表达基因。接着,检测 circ_001287 的表达情况,并选择 circ_001287 表达最高的细胞系进行后续研究。通过荧光素酶报告基因检测、RNA 下拉、RIP、RT-qPCR 和 FISH 鉴定 circ_001287、miR-144 和 CEP55 之间的相互作用。通过 gain-和 loss-of-function 实验,检测 circ_001287 对转染细胞增殖、侵袭和迁移能力以及在小鼠体内致瘤性的影响。

结果

circ_001287 和 CEP55 在 RCC 组织和细胞系中高表达,而 miR-144 则降低。circ_001287 可通过与 miR-144 结合而上调 CEP55,导致增殖、侵袭和迁移能力增强,并促进体内肿瘤生长。此外,下调 miR-144 也观察到促进这些生物学活性。

结论

总之,这些结果阐明了 circ_001287 在 RCC 发生发展中的新机制,并为 RCC 患者提供了潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75f8/7706056/fdb7150caa9e/13046_2020_1744_Fig1_HTML.jpg

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