长链非编码 RNA LINC00200 通过调节 miR-143-3p/SERPINE1 轴抑制胃癌进展。

Knockdown of Long Non-coding RNA LINC00200 Inhibits Gastric Cancer Progression by Regulating miR-143-3p/SERPINE1 Axis.

机构信息

Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu Province, China.

Department of Pathology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu Province, China.

出版信息

Dig Dis Sci. 2021 Oct;66(10):3404-3414. doi: 10.1007/s10620-020-06691-8. Epub 2020 Nov 3.

Abstract

BACKGROUND

An increasing number of studies have found that long non-coding RNAs (lncRNAs) play an important role in carcinogenesis and tumor progression, whereas their molecular mechanisms of function remain largely unknown.

AIMS

This study was aimed to explore the biological function and underlying mechanism of a new lncRNA LINC00200 in gastric cancer (GC).

METHODS

qRT-PCR analysis was conducted to examine the LINC00200 expression level in both GC tissues and cell lines. Functional assays were carried out to detect the effect of LINC00200 on GC cell proliferation, invasion and migration. The interaction between LINC00200 and miR-143-3p was confirmed by luciferase reporter assays. Rescue assays were performed to confirm the influence of LINC00200-miR-143-3p-SERPINE1 axis on GC development.

RESULTS

LINC00200 was found to be upregulated in GC tissues and cell lines. Moreover, knockdown of LINC00200 suppressed GC cell proliferation, invasion and migration in vitro and inhibited tumorigenesis in mouse xenografts. Finally, mechanism research indicated that LINC00200 functioned as a ceRNA to sponge for miR-143-3p, thus leading to the disinhibition of its target gene SERPINE1.

CONCLUSIONS

LINC00200 is significantly overexpressed in GC and accelerates GC progression through regulating miR-143-3p/SERPINE1 axis. Our results may provide a potential diagnostic biomarker and therapeutic target for the management of GC patients.

摘要

背景

越来越多的研究发现长非编码 RNA(lncRNA)在致癌作用和肿瘤进展中发挥重要作用,但其功能的分子机制在很大程度上仍不清楚。

目的

本研究旨在探讨新的 lncRNA LINC00200 在胃癌(GC)中的生物学功能和潜在机制。

方法

采用 qRT-PCR 分析检测 GC 组织和细胞系中 LINC00200 的表达水平。进行功能测定以检测 LINC00200 对 GC 细胞增殖、侵袭和迁移的影响。通过荧光素酶报告基因实验证实 LINC00200 与 miR-143-3p 之间的相互作用。进行挽救实验以确认 LINC00200-miR-143-3p-SERPINE1 轴对 GC 发展的影响。

结果

发现 LINC00200 在 GC 组织和细胞系中上调。此外,敲低 LINC00200 可抑制体外 GC 细胞的增殖、侵袭和迁移,并抑制小鼠异种移植中的肿瘤发生。最后,机制研究表明 LINC00200 作为 ceRNA 与 miR-143-3p 结合,从而导致其靶基因 SERPINE1 失抑制。

结论

LINC00200 在 GC 中显著过表达,并通过调节 miR-143-3p/SERPINE1 轴加速 GC 进展。我们的研究结果可能为 GC 患者的管理提供潜在的诊断生物标志物和治疗靶标。

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