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工程化外泌体介导的hsa-miR-320a转移通过靶向MCL1克服宫颈癌细胞的化疗耐药性

Engineered Exosomes-Mediated Transfer of hsa-miR-320a Overcomes Chemoresistance in Cervical Cancer Cells Targeting MCL1.

作者信息

Zhou Jinling, Wang Yuanhe, Zhang Lizhu, Chen Qin, Zhu Xiaojun, Jiang Peiyue, Jiang Nan, Zhao Wei, Li Baohua

机构信息

Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Institute of Nanjing Nanxin Pharmaceutical Technology Research, Nanjing, China.

出版信息

Front Pharmacol. 2022 Apr 4;13:883445. doi: 10.3389/fphar.2022.883445. eCollection 2022.

Abstract

In cervical cancer (CC), cisplatin resistance greatly restricts the application in clinical. Here, we report that engineered exosomes-mediated transfer of hsa-miR-320a overcomes chemoresistance in cervical cancer cells via targeting Myeloid Cell Leukemia Sequence 1 (MCL1). In DDP resistant CC tissues, as well as cell lines, it was found that miR-320a expression is lower, engineered miR-320a exosomes were used to attenuate DDP resistance in Hela/DDP and Caski/DDP cells. Mechanistically, we find that MCL1, which is a target of miR-320a, overcomes DDP resistance in Hela/DDP cells and in mice. In conclusion, we report that the engineered miR-320a exosomes is proved to be effective and safe.

摘要

在宫颈癌(CC)中,顺铂耐药性极大地限制了其在临床上的应用。在此,我们报告工程化外泌体介导的hsa-miR-320a转移通过靶向髓样细胞白血病序列1(MCL1)克服了宫颈癌细胞的化疗耐药性。在顺铂耐药的CC组织以及细胞系中,发现miR-320a表达较低,工程化的miR-320a外泌体用于减弱Hela/DDP和Caski/DDP细胞中的顺铂耐药性。从机制上讲,我们发现作为miR-320a靶点的MCL1克服了Hela/DDP细胞和小鼠中的顺铂耐药性。总之,我们报告工程化的miR-320a外泌体被证明是有效且安全的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7225/9013939/f3b92448744a/fphar-13-883445-g001.jpg

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