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环状 RNA 003390/真核翻译起始因子 4A3 通过 miR-195-5p 调控血管内皮生长因子信号通路促进子宫内膜癌细胞迁移和增殖

Circ 003390/Eukaryotic translation initiation factor 4A3 promoted cell migration and proliferation in endometrial cancer via vascular endothelial growth factor signaling by miR-195-5p.

机构信息

Department of Gynecology and Obstetrics, The Forth Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

Bioengineered. 2022 May;13(5):11958-11972. doi: 10.1080/21655979.2022.2069358.

Abstract

The differential expression of circRNA in different biological samples renders it as an ideal biomarker for disease diagnosis and identification of tissue development. In addition, the gradual clarification of the mode of action of circRNA in disease makes it as a potential therapeutic target. The purpose of this study is to investigate the role and regulating mechanism of circular RNA has circ 003390 (circWEE1) on Endometrial cancer (EC) genesis. To estimate clinical values of circWEE1 on cell migration and proliferation in EC, and its possible mechanisms. The expression of circWEE1 and EIF4A3in EC cells have been evaluated using qPCR and Western blot. The expression of circWEE1 and EIF4A3 levels were increased in patients with EC. Over-expression of circWEE1 or down-regulation of miR-195-5p promoted cell migration and proliferation in EC. Next, we verified that eIF4A3 binds to the circWEE1 mRNA transcript, circWEE1 served as a sponge that directly targeted miR-195-5p. Bioinformatics prediction forecast that miR-195-5p directly targeted VEGF at 3'-UTR, which was confirmed by luciferase reporter assay. Our findings indicate that Circular RNA hsa circWEE1/EIF4A3 promoted cell migration and proliferation in EC via VEGF signaling by miR-195-5p, which could provide pivotal potential therapeutic targets for the treatment of EC.

摘要

circRNA 在不同生物样本中的差异表达使其成为疾病诊断和组织发育鉴定的理想生物标志物。此外,circRNA 在疾病中的作用模式逐渐阐明,使其成为潜在的治疗靶点。本研究旨在探讨环状 RNA circ 003390(circWEE1)在子宫内膜癌(EC)发生中的作用及其调控机制。评估 circWEE1 在 EC 细胞迁移和增殖中的临床价值及其可能的机制。采用 qPCR 和 Western blot 评估 EC 细胞中 circWEE1 和 EIF4A3 的表达。EC 患者的 circWEE1 和 EIF4A3 水平表达增加。circWEE1 的过表达或 miR-195-5p 的下调促进了 EC 细胞的迁移和增殖。接下来,我们验证了 eIF4A3 与 circWEE1 mRNA 转录本结合,circWEE1 作为直接靶向 miR-195-5p 的海绵。生物信息学预测预测 miR-195-5p 直接靶向 VEGF 的 3'-UTR,荧光素酶报告基因检测证实了这一点。我们的研究结果表明,环状 RNA hsa circWEE1/EIF4A3 通过 miR-195-5p 介导的 VEGF 信号通路促进 EC 细胞的迁移和增殖,这为 EC 的治疗提供了重要的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690d/9276038/d887455ca354/KBIE_A_2069358_UF0001_OC.jpg

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