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长链非编码 RNA TUG1 通过 miR-186-5p/ZEB1 轴促进卵巢癌细胞的增殖、侵袭和干性。

LncRNA TUG1 facilitates proliferation, invasion and stemness of ovarian cancer cell via miR-186-5p/ZEB1 axis.

机构信息

Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

School of Mathematics and Information Science, Jiangxi Normal University, Nanchang, China.

出版信息

Cell Biochem Funct. 2020 Dec;38(8):1069-1078. doi: 10.1002/cbf.3544. Epub 2020 May 11.

Abstract

LncRNA TUG1 has been rarely studied in ovarian cancer (OC), our objective was to explore the role of TUG1 in the regulation of malignant phenotypes of OC. Vectors of sh-TUG1, miR-186-5p and pcDNA-ZEB1 were, respectively, constructed and used to infect OC cells. MTT and transwell assays were applied for representing cell proliferation and invasion, respectively. Sphere formation experiment was used to detect the stemness of OC cells. Western blotting and qRT-PCR were employed for detecting the expression of multiple biomarkers on protein and RNA levels, respectively. The luciferase assay was performed to reveal the interactions between miR-186-5p and TUG1 or ZEB1. The silencing of TUG1 and upregulation of miR-186-5p both suppressed the cell proliferation, invasion and cancer stem cell (CSC) properties. Additionally, luciferase assay verified that miR-186-5p directly binds TUG1 and ZEB1. Moreover, overexpression of ZEB1 rescued the impact on the proliferation, invasion and stemness of TUG1 silencing in OC. TUG1 sponges miR-186-5p to release ZEB1 and promotes the proliferation, invasion and stemness of OC cells, suggesting that TUG1 could be a potential therapeutic target for OC therapy. SIGNIFICANCE OF THE STUDY: LncRNA TUG1 could promote proliferation, invasion and stemness of ovarian cancer cells. Our study first discovered that TUG1 play a tumourigenic role in ovarian cancer by regulating stemness of cancer cells. Mechanism research exhibited the regulation role of TUG1 in ovarian cancer cells was miR-186-5p/ZEB1 axis depended. These results provided a new perspective to understand the pathogenesis and development of ovarian cancer; it will offer new evidence for better diagnosis and treatment therapy of ovarian cancer.

摘要

LncRNA TUG1 在卵巢癌 (OC) 中的研究甚少,我们的目的是探讨 TUG1 在调节 OC 恶性表型中的作用。分别构建了 sh-TUG1、miR-186-5p 和 pcDNA-ZEB1 载体,并用于感染 OC 细胞。MTT 和 Transwell 测定分别用于代表细胞增殖和侵袭。球体形成实验用于检测 OC 细胞的干性。Western blot 和 qRT-PCR 分别用于检测多种生物标志物在蛋白和 RNA 水平上的表达。荧光素酶测定用于揭示 miR-186-5p 与 TUG1 或 ZEB1 之间的相互作用。TUG1 的沉默和 miR-186-5p 的上调均抑制了细胞增殖、侵袭和癌症干细胞 (CSC) 特性。此外,荧光素酶测定证实 miR-186-5p 直接结合 TUG1 和 ZEB1。此外,ZEB1 的过表达挽救了 TUG1 沉默对 OC 增殖、侵袭和干性的影响。TUG1 海绵 miR-186-5p 释放 ZEB1,并促进 OC 细胞的增殖、侵袭和干性,表明 TUG1 可能是 OC 治疗的潜在治疗靶点。研究的意义:LncRNA TUG1 可促进卵巢癌细胞的增殖、侵袭和干性。我们的研究首次发现,TUG1 通过调节癌细胞干性在卵巢癌中发挥致癌作用。机制研究表明,TUG1 对卵巢癌细胞的调节作用依赖于 miR-186-5p/ZEB1 轴。这些结果为理解卵巢癌的发病机制和发展提供了新的视角;为更好地诊断和治疗卵巢癌提供了新的证据。

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