外泌体 miR-3180-3p 通过下调 FOXP4 抑制非小细胞肺癌的增殖和转移。

Exosomal miR-3180-3p inhibits proliferation and metastasis of non-small cell lung cancer by downregulating FOXP4.

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, China.

Department of Pharmacology, Soochow University, Suzhou, China.

出版信息

Thorac Cancer. 2021 Feb;12(3):372-381. doi: 10.1111/1759-7714.13759. Epub 2020 Dec 21.

DOI:10.1111/1759-7714.13759

PMID:33350095

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7862798/

Abstract

BACKGROUND

Non-small cell lung cancer (NSCLC) is one of the most malignant cancers worldwide and its pathogenesis is not completely clear. In this study, we explored the functions and mechanisms of exosomes transferring miR-3180-3p in NSCLC progression.

METHODS

The expression levels of miR-3180-3p in NSCLC tissues and paracarcinoma tissues was obtained from the GEO database (GEO: GSE53882). Exosomes derived from A549 cells were identified. Proliferation, migration and invasion were measured after treatment with exosomal miR-3180-3p or transfection using miR-3180-3p mimics. The relationship between miR-3180-3p and forkhead box P4 (FOXP4) was predicted using a bioinformatic tool and measured using a dual-luciferase reporter gene assay and western blotting. Finally, a mouse xenograft model of NSCLC cells was established to verify the function of exosomal miR-3180-3p in vivo.

RESULTS

We found that miR-3180-3p decreased in both NSCLC cell lines and patient tissues. Overexpression of miR-3180-3p or treatment with exosomal miR-3180-3p significantly suppressed cell proliferation and metastasis in NSCLC cell lines. Subsequently, we found miR-3180-3p downregulated FOXP4 protein expression levels. Furthermore, the volumes and weights of nude mouse tumors expressing exosomal miR-3180-3p were significantly reduced.

CONCLUSIONS

Exosomal miR-3180-3p suppresses NSCLC progression by downregulating FOXP4 expression.

KEY POINTS

SIGNIFICANT FINDINGS OF THE STUDY: We found that exosomal miR-3180-3p suppressed NSCLC progression and also identified a miR-3180-3p target gene. These findings provide a foundation to determine innovative therapeutic strategies.

WHAT THIS STUDY ADDS

This study contributes to research investigating exosomal containing miRNAs.

摘要

背景

非小细胞肺癌（NSCLC）是全球最恶性的癌症之一，其发病机制尚不完全清楚。在本研究中，我们探讨了外泌体传递 miR-3180-3p 在 NSCLC 进展中的功能和机制。

方法

从 GEO 数据库（GEO：GSE53882）中获取 NSCLC 组织和癌旁组织中 miR-3180-3p 的表达水平。鉴定来源于 A549 细胞的外泌体。用外泌体 miR-3180-3p 或 miR-3180-3p 模拟物转染处理后，测量增殖、迁移和侵袭。使用生物信息学工具预测 miR-3180-3p 与叉头框 P4（FOXP4）之间的关系，并使用双荧光素酶报告基因检测和 Western blot 进行测量。最后，建立 NSCLC 细胞的小鼠异种移植模型，以验证外泌体 miR-3180-3p 在体内的功能。

结果

我们发现 miR-3180-3p 在 NSCLC 细胞系和患者组织中均降低。miR-3180-3p 的过表达或用外泌体 miR-3180-3p 处理可显著抑制 NSCLC 细胞系中的细胞增殖和转移。随后，我们发现 miR-3180-3p 下调了 FOXP4 蛋白表达水平。此外，表达外泌体 miR-3180-3p 的裸鼠肿瘤的体积和重量明显减轻。