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骨髄间充质干细胞来源的外泌体 miR-101-3p 通过调控 EZH2 水平促进非小细胞肺癌放射敏感性及对 DNA 损伤修复和自噬的影响

Exosome miR-101-3p derived from bone marrow mesenchymal stem cells promotes radiotherapy sensitivity in non-small cell lung cancer by regulating DNA damage repair and autophagy levels through EZH2.

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.

Department of Oncology Radiotherapy, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.

出版信息

Pathol Res Pract. 2024 Apr;256:155271. doi: 10.1016/j.prp.2024.155271. Epub 2024 Mar 28.

DOI:10.1016/j.prp.2024.155271

PMID:38574630

Abstract

BACKGROUND AND OBJECTIVE

The morbidity rate of non-small cell lung cancer (NSCLC) increases with age, highlighting that NSCLC is a serious threat to human health. The aim of this study was mainly to describe the role of exosomal miR-101-3p derived from bone marrow mesenchymal stem cells (BMSCs) in NSCLC.

METHODS

A549 or NCI-H1703 cells (1×10/mouse) were injected into nude mice to establish an NSCLC animal model. RTqPCR, Western blotting and comet assays were used to assess the changes in gene expression, proteins and DNA damage repair.

RESULTS

miR-101-3p and RAI2 were found to be expressed at low levels in NSCLC, while EZH2 was highly expressed. In terms of function, miR-101-3p downregulated EZH2. In addition, exosomal miR-101-3p derived from BMSCs promoted the expression of RAI2, inhibited DNA damage repair, and inhibited the activation of the PI3K/AKT/mTOR signaling pathway by inhibiting EZH2, thereby promoting autophagy and decreasing cell viability and finally enhancing the sensitivity of NSCLC to radiotherapy and inhibiting the malignant biological behavior of NSCLC.

CONCLUSION

Exosomal miR-101-3p derived from BMSCs can inhibit DNA damage repair, promote autophagy, enhance the radiosensitivity of NSCLC, and inhibit the progression of NSCLC by inhibiting EZH2.

摘要

背景与目的

非小细胞肺癌（NSCLC）的发病率随年龄增长而升高，表明 NSCLC 严重威胁人类健康。本研究主要旨在描述骨髓间充质干细胞（BMSC）来源的外泌体 miR-101-3p 在 NSCLC 中的作用。

方法

将 A549 或 NCI-H1703 细胞（1×10/只小鼠）注射到裸鼠中建立 NSCLC 动物模型。采用 RTqPCR、Western blot 和彗星试验检测基因表达、蛋白和 DNA 损伤修复的变化。

结果

miR-101-3p 和 RAI2 在 NSCLC 中表达水平较低，而 EZH2 表达水平较高。在功能方面，miR-101-3p 下调 EZH2。此外，BMSC 来源的外泌体 miR-101-3p 促进 RAI2 的表达，抑制 DNA 损伤修复，并通过抑制 EZH2 抑制 PI3K/AKT/mTOR 信号通路的激活，从而促进自噬，降低细胞活力，最终增强 NSCLC 对放疗的敏感性，并抑制 NSCLC 的恶性生物学行为。