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环状 RNA_0005075 通过调控 miR-431/p53/上皮-间质转化轴抑制胃癌发生。

CircRNA_0005075 suppresses carcinogenesis via regulating miR-431/p53/epithelial-mesenchymal transition axis in gastric cancer.

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, China.

出版信息

Cell Biochem Funct. 2020 Oct;38(7):932-942. doi: 10.1002/cbf.3519. Epub 2020 Mar 4.

Abstract

This study was aimed to explore the expression and biological function of circRNA_0005075 in gastric cancer (GC) progression and its underlying mechanism. First, the expression level of circRNA_0005075 and microRNA-431 (miR-431) in GC tissues were detected with the quantitative real-time polymerase chain reaction. In addition, after down-regulated the circRNA_0005075 expression by plasmid transfection in GC cells, the Cell Counting Kit-8 (CCK-8), EDU, transwell assay were conducted to evaluate the function of circRNA_0005075 or miR-431 on cell proliferation, metastasis in vitro. Moreover, p53 and Epithelial-mesenchymal transition (EMT) pathway related proteins were also measured with western blotting. Then, our data revealed that CircRNA_0005075 was found to be significantly up-regulated in GC tissues as well as GC cell lines, and the GC patients with higher CircRNA_0005075 expression were more likely to have poor outcomes. Down-regulation of CircRNA_0005075 could significantly suppress the GC cell proliferation and cell metastasis ability, while the addition of miR-431 inhibitors could counteract this effect. Importantly, we discovered that the silencing of circRNA_0005075 could weaken the micro-RNA sponge function for miR-431, and then upregulate the expression of p53 and forbid the EMT signalling pathway, and finally suppress the tumourigenesis of GC. To sum up, CircRNA_0005075 could inhibit cell growth and metastasis of GC through regulating the miR-431/p53/EMT axis. SIGNIFICANCE OF THE STUDY: The research clearly elucidated the potential role and relative regulatory mechanism of circRNA_0005075 in gastric cancer (GC) progression. Briefly, circRNA_0005075 could directly inhibit the expression level of miR-431, then regulate the p53/Epithelial-mesenchymal transition axis, and finally inhibit cell growth and metastasis in GC. Consequently, circRNA_0005075 might act as an oncogene in the GC procession, which provides a promising way for the treatment of GC.

摘要

本研究旨在探讨环状 RNA_0005075 在胃癌(GC)进展中的表达和生物学功能及其潜在机制。首先,采用实时定量聚合酶链反应检测 GC 组织中环状 RNA_0005075 和 microRNA-431(miR-431)的表达水平。此外,通过质粒转染下调 GC 细胞中环状 RNA_0005075 的表达后,通过细胞计数试剂盒-8(CCK-8)、EDU、Transwell 测定评估环状 RNA_0005075 或 miR-431 对细胞增殖、体外转移的功能。此外,还通过蛋白质印迹法测量了 p53 和上皮-间充质转化(EMT)途径相关蛋白。然后,我们的数据表明,环状 RNA_0005075 在 GC 组织和 GC 细胞系中均明显上调,GC 患者中环状 RNA_0005075 表达较高者预后较差。下调环状 RNA_0005075 可显著抑制 GC 细胞增殖和细胞转移能力,而添加 miR-431 抑制剂可拮抗此作用。重要的是,我们发现沉默环状 RNA_0005075 可以减弱其对 miR-431 的微 RNA 海绵功能,从而上调 p53 的表达并抑制 EMT 信号通路,最终抑制 GC 的肿瘤发生。总之,环状 RNA_0005075 通过调节 miR-431/p53/EMT 轴抑制 GC 细胞的生长和转移。研究意义:本研究清楚地阐明了环状 RNA_0005075 在胃癌(GC)进展中的潜在作用及其相对调节机制。简要地说,环状 RNA_0005075 可以直接抑制 miR-431 的表达水平,然后调节 p53/上皮-间充质转化轴,最终抑制 GC 中的细胞生长和转移。因此,环状 RNA_0005075 可能在 GC 进展过程中作为癌基因发挥作用,为 GC 的治疗提供了有希望的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85d1/7587004/16c2ce3e9f9a/CBF-38-932-g001.jpg

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