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下调的长链非编码 RNA UCA1 作为 ceRNA 通过降低 ZEB2 表达来吸附 microRNA-498,从而抑制食管癌细胞的增殖、侵袭和上皮间质转化。

Downregulated lncRNA UCA1 acts as ceRNA to adsorb microRNA-498 to repress proliferation, invasion and epithelial mesenchymal transition of esophageal cancer cells by decreasing ZEB2 expression.

机构信息

Department of Oncology, Taizhou People's Hospital , Taizhou , PR. China.

Anesthesiology Department, Taizhou People's Hospital , Taizhou , PR. China.

出版信息

Cell Cycle. 2019 Sep;18(18):2359-2376. doi: 10.1080/15384101.2019.1648959. Epub 2019 Aug 6.

Abstract

: Esophageal cancer (EC) is one of the most general malignant tumors in humans. There were few studies researching the connections between lncRNA UCA1 and EC. This study is to research the effect of lncRNA UCA1 adsorbing microRNA-498 (miR-498) as a ceRNA to regulate ZEB2 expression on epithelial mesenchymal transition (EMT), invasion and migration of EC cells. : UCA1, miR-498 and ZEB2 expression in EC tissues and cells was detected by RT-qPCR or western blot analysis. EC cells were transfected with siRNA-UCA1, miR-498 mimics or their controls to determine cell colony, proliferation, cycle distribution, apoptosis, migration and invasion by colony formation assay, CCK-8 assay, flow cytometry, and Transwell assay, respectively. The protein expression of PCNA, c-Myc, E-cadherin, N-cadherin, MMP-2 and MMP-9 was detected by Western blot analysis. The growth rate and weight of transplanted tumor in nude mice were observed. : There were overly expressed UCA1 and ZEB2 and lowly expressed miR-498 in EC tissues and cells. LncRNA UCA1 acted as ceRNA to inhibit miR-498 expression and thereby increasing ZEB2 expression. With down-regulated UCA1 and up-regulated miR-498, ZEB2 expression, cell proliferation, colony formation, invasion, migration ability, EMT, tumor growth rate and weight in nude mice were apparently reduced. : This study demonstrates that inhibited UCA1 up-regulated miR-498 and down-regulated ZEB2, thereby repressing proliferation activity, invasion, migration, and EMT of EC cells.

摘要

食管癌(EC)是人类最常见的恶性肿瘤之一。很少有研究探讨 lncRNA UCA1 与 EC 之间的关系。本研究旨在研究 lncRNA UCA1 通过作为 ceRNA 吸附 microRNA-498(miR-498)来调节 EC 细胞上皮间质转化(EMT)、侵袭和迁移过程中 ZEB2 表达的作用。

通过 RT-qPCR 或 Western blot 分析检测 EC 组织和细胞中的 UCA1、miR-498 和 ZEB2 表达。通过集落形成实验、CCK-8 实验、流式细胞术和 Transwell 实验分别用 siRNA-UCA1、miR-498 模拟物或其对照转染 EC 细胞,以确定细胞集落、增殖、细胞周期分布、凋亡、迁移和侵袭。Western blot 分析检测 PCNA、c-Myc、E-钙黏蛋白、N-钙黏蛋白、MMP-2 和 MMP-9 的蛋白表达。观察裸鼠移植瘤的生长速度和重量。

EC 组织和细胞中存在 UCA1 过表达、ZEB2 过表达和 miR-498 低表达。lncRNA UCA1 作为 ceRNA 抑制 miR-498 的表达,从而增加 ZEB2 的表达。下调 UCA1 和上调 miR-498 后,ZEB2 表达、细胞增殖、集落形成、侵袭、迁移能力、EMT、裸鼠肿瘤生长速度和重量明显降低。

本研究表明,抑制 UCA1 可上调 miR-498,下调 ZEB2,从而抑制 EC 细胞的增殖活性、侵袭、迁移和 EMT。

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