负载抗癌分子mir-1-3p的外泌体可抑制人食管鳞状癌细胞在肺内的定植和生长。

Exosomes loaded with the anti-cancer molecule mir-1-3p inhibit intrapulmonary colonization and growth of human esophageal squamous carcinoma cells.

作者信息

Yu Yanmei, Jin Bingjie, Jia Ruzhen, Shi Lei, Chen Yong, Ge Jian, Xu Changqin

机构信息

Ultrasonography Department, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.

Gastroenterology Department, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No.324 JingwuWeiqi Road, Jinan, Shandong, 250021, China.

出版信息

J Transl Med. 2024 Dec 31;22(1):1166. doi: 10.1186/s12967-024-05997-9.

DOI:10.1186/s12967-024-05997-9

PMID:39741298

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11687107/

Abstract

BACKGROUND

The overall prognosis of patients with esophageal cancer (EC) is extremely poor. There is an urgent need to develop innovative therapeutic strategies. This study will investigate the anti-cancer effects of exosomes loaded with specific anti-cancer microRNAs in vivo and in vitro.

METHODS

Specific miRNAs that were significantly down-regulated in EC tissues were screened using the miRNAs profiling data of human EC tissue samples in TCGA, and the role of their exogenous expression in the proliferation and migration of human EC cell lines, KYSE150 and Eca109, were detected using CCK-8 and Transwell assays. Exosomes were loaded with miRNAs using electroporation.

RESULTS

The expression of miR-1-3p was significantly down-regulated in human EC tissues with potential anti-cancer effects. Exosomes loaded with miR-1-3p significantly inhibited the proliferation, migration and invasion of KYSE150 and Eca109 cells in vitro, as well as the intrapulmonary colonization and growth of KYSE150 cells in vivo. In addition, miR-1-3p could directly bind to the 3'UTR of the transcription factor E2F5 mRNA, down-regulate the protein expression of E2F5, and inhibit the activation of the MAPK/ERK signaling pathway.

CONCLUSION

Exosomes loaded with miR-1-3p may be applicable to the treatment of EC.

摘要

背景

食管癌（EC）患者的总体预后极差。迫切需要开发创新的治疗策略。本研究将在体内和体外研究负载特定抗癌微小RNA的外泌体的抗癌作用。

方法

利用TCGA中人类EC组织样本的微小RNA谱数据筛选出在EC组织中显著下调的特定微小RNA，并使用CCK-8和Transwell实验检测其外源表达对人类EC细胞系KYSE150和Eca109增殖和迁移的作用。通过电穿孔法将微小RNA负载到外泌体中。

结果

miR-1-3p的表达在具有潜在抗癌作用的人类EC组织中显著下调。负载miR-1-3p的外泌体在体外显著抑制KYSE150和Eca109细胞的增殖、迁移和侵袭，以及体内KYSE150细胞的肺内定植和生长。此外，miR-1-3p可直接结合转录因子E2F5 mRNA的3'UTR，下调E2F5的蛋白表达，并抑制MAPK/ERK信号通路的激活。