Rab27b-mediated CAFs derived exosomal miR-22-3p suppresses ferroptosis and promotes cisplatin resistance in osteosarcoma

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-09-17 DOI:10.1016/j.cellsig.2025.112125

Wenyuan Duan , Xiaoying Niu , Yunsong Liu , Wen Tian

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引用次数: 0

Abstract

Chemoresistance remains a significant hurdle in the cisplatin treatment of osteosarcoma, with poor patient outcomes. Cancer-associated fibroblasts (CAFs) and exosomes play crucial roles in this resistance by transferring miRNAs to cancer cells. In this study, we investigated the biological role of CAFs derived exosomal miR-22-3p in promoting chemoresistance. Using single-cell analysis and tissue exosome miRNAs sequencing, CAFs derived exosomal miR-22-3p was significantly associated with cisplatin resistance. Using various co-culture models, we showed the regulatory function of Rab27b and CAFs derived exosomal miR-22-3p, as well as the inhibitory effect of miR-22-3p on PTEN and ferroptosis. Experiments in vivo validated that CAFs derived exosomal miR-22-3p downregulated ferroptosis and promoted resistance to cisplatin. Overall, our findings suggest that targeting the Rab27b/exosomal miR-22-3p/PTEN/ferroptosis axis could be a promising therapeutic strategy for overcoming chemoresistance in osteosarcoma by providing critical insights into the role of exosome-mediated communication within the tumor microenvironment.

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rab27b介导的CAFs来源的外泌体miR-22-3p抑制骨肉瘤中的铁下沉并促进顺铂耐药性。

化疗耐药仍然是顺铂治疗骨肉瘤的一个重要障碍，患者预后较差。癌症相关成纤维细胞（CAFs）和外泌体通过将mirna转移到癌细胞中，在这种耐药性中发挥关键作用。在这项研究中，我们研究了CAFs来源的外泌体miR-22-3p在促进化疗耐药中的生物学作用。通过单细胞分析和组织外泌体miRNAs测序，CAFs来源的外泌体miR-22-3p与顺铂耐药显著相关。通过多种共培养模型，我们展示了Rab27b和CAFs衍生的外泌体miR-22-3p的调控功能，以及miR-22-3p对PTEN和铁吊的抑制作用。体内实验证实，CAFs衍生的外泌体miR-22-3p下调铁下垂并促进对顺铂的耐药。总之，我们的研究结果表明，靶向Rab27b/外泌体miR-22-3p/PTEN/ferroptosis轴可能是克服骨肉瘤化疗耐药的一种有希望的治疗策略，为肿瘤微环境中外泌体介导的通讯的作用提供了重要的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.