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环状 RNA circ0005654 通过与 microRNA-363 结合特异性蛋白 1 促进胃癌进展。

The circular RNA circ0005654 interacts with specificity protein 1 via microRNA-363 sequestration to promote gastric cancer progression.

机构信息

Department of Clinical Medicine, Wanxi Health Vocational College, Lu'an, Anhui, P.R. China.

Department of Emergency Surgery, Lu'an People's Hospital, Lu'an, Anhui, P.R. China.

出版信息

Bioengineered. 2021 Dec;12(1):6305-6317. doi: 10.1080/21655979.2021.1971031.

Abstract

Circular RNAs (circRNAs), a group of unique long noncoding RNAs, are involved in gastric carcinogenesis through multiple mechanisms, including interacting with microRNAs (miRNAs). Here, circ0005654, significantly upregulated in gastric cancer (GC), was chosen for further examination. circ0005654 was analyzed by RT-qPCR. The function of circ0005654 in GC cells was substantiated by loss-of-function assays. The mechanism of circ0005654 on miR-363/specificity protein 1 (sp1) axis was evaluated in GC cells by bioinformatics analysis, luciferase reporter, FISH, and ChIP assays. We observed that circ0005654 was enhanced in GC tissues and cells. Overexpression of circ0005654 was correlated with a poor long-term prognosis in patients with GC. Functionally, silencing of circ0005654 remarkably suppressed GC cell proliferation, migration and invasiveness and tumorigenesis and metastases . It was also established that circ0005654 served as a miR-363 sponge and enhanced sp1 expression. Furthermore, sp1 promoted GC carcinogenesis by regulating myc transcription to potentiate the Wnt/β-catenin pathway. In conclusion, circ0005654 expedites the GC development via miR-363/sp1/myc/Wnt/β-catenin axis and is a new biomarker for GC treatment regimen.

摘要

环状 RNA(circRNAs)是一组独特的长非编码 RNA,通过多种机制参与胃癌的发生,包括与 microRNA(miRNAs)相互作用。在这里,circ0005654 在胃癌(GC)中显著上调,被选择进一步研究。通过 RT-qPCR 分析 circ0005654。通过功能丧失实验证实了 circ0005654 在 GC 细胞中的功能。通过生物信息学分析、荧光素酶报告基因、FISH 和 ChIP 实验评估了 circ0005654 在 GC 细胞中对 miR-363/特异性蛋白 1(sp1)轴的作用机制。我们观察到 circ0005654 在 GC 组织和细胞中增强。circ0005654 的过表达与 GC 患者的不良长期预后相关。功能上,沉默 circ0005654 显著抑制 GC 细胞的增殖、迁移和侵袭以及肿瘤的发生和转移。还发现 circ0005654 作为 miR-363 的海绵并增强 sp1 表达。此外,sp1 通过调节 myc 转录来增强 Wnt/β-catenin 通路,从而促进 GC 癌变。总之,circ0005654 通过 miR-363/sp1/myc/Wnt/β-catenin 轴加速 GC 的发展,是 GC 治疗方案的新生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6e0/8806801/894714531f89/KBIE_A_1971031_F0001_OC.jpg

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