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Circ_0005875 sponges miR-502-5p to promote renal cell carcinoma progression through upregulating E26 transformation specific-1.
Anti-Cancer Drugs ( IF 2.3 ) Pub Date : 2021-08-16 , DOI: 10.1097/cad.0000000000001205
Sheng Luo 1 , Fang Deng 2 , Nana Yao 2 , Fu Zheng 3
Affiliation  

Increasing evidence has shown that circular RNAs (circRNAs) play critical roles in various cancers, including renal cell carcinoma (RCC). We aimed to explore the role and underlying mechanism of circ_0005875 in RCC. The expression levels of circ_0005875, microRNA-502-5p (miR-502-5p) and E26 transformation specific-1 (ETS1) mRNA were determined by quantitative real-time PCR. Cell proliferation was assessed by Cell Counting Kit-8, colony formation, and 5-Ethynyl-2'-deoxyuridine (EdU) assays. Cell migration and invasion were monitored by wound healing assay and transwell assay, respectively. Flow cytometry analysis was applied to determine cell apoptosis and cell cycle distribution. Western blot assay was performed to measure the protein expression of CyclinD1 and ETS1. The interaction between miR-502-5p and circ_0005875 or ETS1 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. A xenograft tumor model was established to confirm the role of circ_0005875 in vivo. Circ_0005875 and ETS1 were upregulated and miR-502-5p was downregulated in RCC tissues and cells. Knockdown of circ_0005875 suppressed RCC cell proliferation, migration and invasion, and induced apoptosis and cell cycle arrest. MiR-502-5p was a target of circ_0005875, and miR-502-5p inhibition reversed the inhibitory effects of circ_0005875 knockdown on the malignant behaviors of RCC cells. ETS1 was a direct target of miR-502-5p, and miR-502-5p exerted its anti-tumor role in RCC cells by targeting ETS1. Moreover, circ_0005875 knockdown decreased ETS1 expression by sponging miR-502-5p. Additionally, circ_0005875 depletion suppressed tumor growth in vivo. Circ_0005875 knockdown suppressed RCC progression by regulating miR-502-5p/ETS1 axis, which might provide a promising therapeutic target for RCC.

中文翻译:

Circ_0005875 海绵 miR-502-5p 通过上调 E26 转化特异性 1 促进肾细胞癌进展。

越来越多的证据表明,环状 RNA (circRNA) 在包括肾细胞癌 (RCC) 在内的各种癌症中发挥着关键作用。我们的目的是探讨circ_0005875在RCC中的作用和潜在机制。通过定量实时 PCR 测定 circ_0005875、microRNA-502-5p (miR-502-5p) 和 E26 转化特异性 1 (ETS1) mRNA 的表达水平。通过 Cell Counting Kit-8、集落形成和 5-乙炔基-2'-脱氧尿苷 (EdU) 测定评估细胞增殖。分别通过伤口愈合测定和transwell测定监测细胞迁移和侵袭。应用流式细胞术分析确定细胞凋亡和细胞周期分布。采用Western blot法检测CyclinD1和ETS1的蛋白表达。通过双荧光素酶报告基因和 RNA 免疫沉淀测定证实了 miR-502-5p 与 circ_0005875 或 ETS1 之间的相互作用。建立异种移植肿瘤模型以证实circ_0005875在体内的作用。RCC 组织和细胞中 Circ_0005875 和 ETS1 上调,miR-502-5p 下调。circ_0005875 的敲低抑制了 RCC 细胞的增殖、迁移和侵袭,并诱导细胞凋亡和细胞周期停滞。miR-502-5p是circ_0005875的靶标,miR-502-5p抑制逆转了circ_0005875敲低对RCC细胞恶性行为的抑制作用。ETS1是miR-502-5p的直接靶标,miR-502-5p通过靶向ETS1在RCC细胞中发挥抗肿瘤作用。此外,circ_0005875 敲低通过海绵 miR-502-5p 降低了 ETS1 表达。此外,circ_0005875 消耗抑制了体内肿瘤生长。Circ_0005875 敲除通过调节 miR-502-5p/ETS1 轴抑制 RCC 进展,这可能为 RCC 提供有希望的治疗靶点。
更新日期:2021-08-16
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