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微小 RNA-590 通过靶向低密度脂蛋白受体相关蛋白 6 抑制食管鳞癌细胞的迁移、侵袭和上皮-间充质转化。

MicroRNA‑590 inhibits migration, invasion and epithelial‑to‑mesenchymal transition of esophageal squamous cell carcinoma by targeting low‑density lipoprotein receptor‑related protein 6.

机构信息

Department of Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450007, P.R. China.

Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.

出版信息

Oncol Rep. 2020 Oct;44(4):1385-1392. doi: 10.3892/or.2020.7692. Epub 2020 Jul 15.

Abstract

MicroRNA‑590 (miR‑590) has been revealed as a tumor suppressor, while low‑density lipoprotein receptor‑related protein 6 (LRP6) is considered to act as a tumor promoter. However, their roles and underlying molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC) have yet to be fully elucidated. Therefore, the present study aimed to investigate these mechanisms. The expression levels of miR‑590 and LRP6 in human ESCC samples and cell lines were determined using reverse transcription‑quantitative PCR. Bioinformatics analysis was used to predict the relationship between miR‑590 and LRP6, and luciferase assay was performed to validate the relationship between these factors. Transwell assays were used to determine cell migration and invasion, while western blotting assays were used to detect the protein expression levels of LRP6, E‑cadherin, N‑cadherin and Vimentin. The present study demonstrated that miR‑590 was downregulated and LRP6 was upregulated in ESCC tissues and cell lines. Furthermore, it was found that miR‑590 overexpression and LRP6 knockdown inhibited cell migration, invasion and epithelial‑to‑mesenchymal transition (EMT) in ESCC cell lines. Additional mechanistic studies identified that LRP6 was a target of, and was inhibited by, miR‑590. Collectively, the present findings suggested that miR‑590 inhibited the invasion, migration and EMT of ESCC cells by mediating LRP6.

摘要

微小 RNA-590 (miR-590) 已被证明是一种肿瘤抑制因子,而低密度脂蛋白受体相关蛋白 6 (LRP6) 被认为是一种肿瘤促进因子。然而,它们在食管鳞状细胞癌 (ESCC) 中的作用和潜在的分子调控机制尚未完全阐明。因此,本研究旨在探讨这些机制。采用逆转录-定量 PCR 检测人 ESCC 组织和细胞系中 miR-590 和 LRP6 的表达水平。采用生物信息学分析预测 miR-590 和 LRP6 之间的关系,并通过荧光素酶报告基因实验验证两者之间的关系。采用 Transwell 实验检测细胞迁移和侵袭能力,采用 Western blot 实验检测 LRP6、E-钙黏蛋白、N-钙黏蛋白和波形蛋白的蛋白表达水平。本研究表明,miR-590 在 ESCC 组织和细胞系中表达下调,LRP6 表达上调。此外,还发现 miR-590 过表达和 LRP6 敲低抑制 ESCC 细胞系的迁移、侵袭和上皮-间充质转化 (EMT)。进一步的机制研究表明,LRP6 是 miR-590 的靶基因,并受到 miR-590 的抑制。综上所述,本研究结果表明,miR-590 通过调节 LRP6 抑制 ESCC 细胞的侵袭、迁移和 EMT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd1/7448422/4dcb6176fbc9/OR-44-04-1385-g00.jpg

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