外泌体衍生的微RNA-221-3p通过调节PIK3r1介导的糖代谢使乳腺癌细胞对阿霉素脱敏

IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Cancer Biotherapy and Radiopharmaceuticals Pub Date : 2024-08-01 Epub Date: 2024-03-26 DOI:10.1089/cbr.2023.0123
Xiaolu Hong, Xiaoping Pan
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引用次数: 0

摘要

背景:癌症衍生的外泌体通过转移 RNA 促进化疗耐药性,但它们在外泌体 microRNA-221-3p (miR-221-3p) 调节乳腺癌(BC)阿霉素耐药性中的作用仍不清楚。研究方法通过递增阿霉素暴露,从MCF-7和MDA-MB-231细胞中培养出阿霉素耐药的乳腺癌细胞。采用定量反转录聚合酶链反应对 miR-221-3p 水平进行定量。随后,分离外泌体并将其与 BC 细胞培养,使用细胞计数试剂盒-8、集落形成和流式细胞术检测法评估外泌体介导的阿霉素敏感性。敏感细胞与 miR-221-3p 抑制剂处理过的细胞共培养,以评估阿霉素耐药性。此外,miR-221-3p 和磷酸肌醇-3-激酶调节亚基 1(PIK3R1)之间的相互作用也通过双荧光素酶报告基因检测得到了验证。模拟物和抑制剂被用来确定 miR-221-3p 对阿霉素耐药性的影响。结果在阿霉素耐药的BC细胞和外泌体中观察到miR-221-3p表达水平升高。敏感细胞与耐药细胞的外泌体共培养后,半数最大抑制浓度值和增殖增加,阿霉素诱导的细胞凋亡减少。然而,在阿霉素耐药细胞中转染 miR-221-3p 抑制剂后,敏感细胞与阿霉素耐药细胞共培养的效果明显减弱。miR-221-3p 抑制剂增加了 PIK3R1、p-AKT、c-Myc、HK2 和 PKM2 的表达,降低了 FOXO3 的表达,削弱了耐药细胞对阿霉素的耐药性。结论:miR-221-3p可通过外泌体在BC细胞间转移。高水平的miR-221-3p可靶向PIK3R1,并促进BC细胞对阿霉素的耐药性。[图:见正文]。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exosome-Derived MicroRNA-221-3p Desensitizes Breast Cancer Cells to Adriamycin by Regulating PIK3r1-Mediated Glycose Metabolism.

Background: Cancer-derived exosomes facilitate chemoresistance by transferring RNAs, yet their role in exosomal microRNA-221-3p (miR-221-3p) regulation of adriamycin resistance in breast cancer (BC) remains unclear. Methods: Adriamycin-resistant BC cells were developed from MCF-7 and MDA-MB-231 cells by incremental adriamycin exposure. The miR-221-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction. Subsequently, exosomes were isolated and incubated with BC cells, and exosome-mediated adriamycin sensitivity was evaluated using Cell Counting Kit-8, colony formation, and flow cytometry assays. Sensitive cells were cocultured with miR-221-3p inhibitor-treated cells to assess adriamycin resistance. Moreover, the interaction between miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was validated using a dual luciferase reporter gene assay. Mimics and inhibitors were used to determine the effects of miR-221-3p on adriamycin resistance. Results: Elevated levels of miR-221-3p expression were observed in adriamycin-resistant BC cells and exosomes. Sensitive cells were cocultured with exosomes from resistant cells, resulting in increased half-maximal inhibitory concentration value and proliferation, and reduced adriamycin-induced apoptosis. However, the effects of coculturing sensitive cells with adriamycin-resistant cells were significantly weakened by miR-221-3p inhibitor transfection in adriamycin-resistant cells. PIK3R1 was found to be a target of miR-221-3p, and miR-221-3p mimics enhanced adriamycin resistance in sensitive cells. miR-221-3p inhibitors increased the expression of PIK3R1, p-AKT, c-Myc, HK2, and PKM2, decreased FOXO3 expression, and weakened the adriamycin resistance in resistant cells. Conclusions: miR-221-3p can be transferred between BC cells through exosomes. High levels of miR-221-3p were found to target PIK3R1 and promoted adriamycin resistance in BC cells. [Figure: see text].

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来源期刊
CiteScore
7.80
自引率
2.90%
发文量
87
审稿时长
3 months
期刊介绍: Cancer Biotherapy and Radiopharmaceuticals is the established peer-reviewed journal, with over 25 years of cutting-edge content on innovative therapeutic investigations to ultimately improve cancer management. It is the only journal with the specific focus of cancer biotherapy and is inclusive of monoclonal antibodies, cytokine therapy, cancer gene therapy, cell-based therapies, and other forms of immunotherapies. The Journal includes extensive reporting on advancements in radioimmunotherapy, and the use of radiopharmaceuticals and radiolabeled peptides for the development of new cancer treatments.
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