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长链非编码 RNA MALAT1 通过调节 miR-200a-3p/程序性死亡配体 1 轴促进非小细胞肺癌进展。

LncRNA MALAT1 contributes to non-small cell lung cancer progression via modulating miR-200a-3p/programmed death-ligand 1 axis.

机构信息

1 Department of Pulmonary and Critical Care Medicine, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, China.

2 Department of Pathology, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, China.

出版信息

Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738419859699. doi: 10.1177/2058738419859699.

Abstract

This study was to investigate the expression correlation between long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1), miR-200a-3p and programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), and their roles in NSCLC. Real-time polymerase chain reaction (PCR) was performed to detect the expressions of MALAT1, miR-200a-3p and PD-L1 in NSCLC tissues and cells for the correlation analysis. The starBase and Targetscan databases were used to predict the binding sites between MALAT1 and miR-200a-3p, and miR-200a-3p and PD-L1, respectively. The targeting relationship between MALAT1 and miR-200a-3p, and miR-200a-3p and PD-L1 were further verified by real-time PCR and dual luciferase reporter gene assay. Cell proliferation was monitored by CCK8 and colony formation assays. The apoptosis was detected using flow cytometry. Wound healing assay and transwell assay were conducted to determine cell migration and invasion. In this study, we demonstrated that in NSCLC tissues, the expression level of MALAT1 was negatively correlated with that of miR-200a-3p, while positively correlated with PD-L1. Besides, MALAT1 promoted proliferation, mobility, migration, and invasion of NSCLC cells via sponging miR-200a-3p. PD-L1 was validated as a target of miR-200a-3p, and indirectly modulated by MALAT1. In conclusion, LncRNA MALAT1 facilitates the progression of NSCLC by modulating miR-200a-3p/PDL1 axis.

摘要

本研究旨在探讨长链非编码 RNA 转移相关肺腺癌转录本 1(lncRNA MALAT1)、miR-200a-3p 与程序性死亡配体 1(PD-L1)在非小细胞肺癌(NSCLC)中的表达相关性及其在 NSCLC 中的作用。采用实时聚合酶链反应(PCR)检测 NSCLC 组织和细胞中 MALAT1、miR-200a-3p 和 PD-L1 的表达情况,并进行相关性分析。利用 starBase 和 Targetscan 数据库分别预测 MALAT1 与 miR-200a-3p、miR-200a-3p 与 PD-L1 的结合位点。进一步通过实时 PCR 和双荧光素酶报告基因检测验证 MALAT1 与 miR-200a-3p、miR-200a-3p 与 PD-L1 的靶向关系。采用 CCK8 和集落形成实验检测细胞增殖,流式细胞术检测细胞凋亡,划痕愈合实验和 Transwell 实验检测细胞迁移和侵袭。本研究表明,在 NSCLC 组织中,MALAT1 的表达水平与 miR-200a-3p 呈负相关,与 PD-L1 呈正相关。此外,MALAT1 通过海绵吸附 miR-200a-3p 促进 NSCLC 细胞的增殖、迁移和侵袭。PD-L1 被验证为 miR-200a-3p 的靶基因,并且可被 MALAT1 间接调控。总之,长链非编码 RNA MALAT1 通过调节 miR-200a-3p/PDL1 轴促进 NSCLC 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58d7/6595645/fbad447ebbd6/10.1177_2058738419859699-fig1.jpg

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