Chemoresistance has been a major challenge in advanced gastric cancer (GC) therapy. Exosomal transfer of oncogenic miRNAs implicates important effects in mediating recipient cell chemoresistance by transmitting active molecules. In this study, we found that microRNA‐500a‐3p was highly expressed in cisplatin (DDP) resistant GC cells (MGC803/DDP and MKN45/DDP) and their secreted exosomes than that in the corresponding parental cells. MGC803/DDP‐derived exosomes enhance DDP resistance and stemness properties of MGC803 recipient cells via exosomal delivery of miR‐500a‐3p in vitro and in vivo through targeting FBXW7. However, reintroduction of FBXW7 in MGC803 cells reverses miR‐500a‐3p‐mediated DDP resistance as well as stemness properties. Furthermore, elevated miR‐500a‐3p in the plasma exosomes of GC patients is correlated with DDP resistance and thereby results in poor progression‐free prognosis. Our finding highlights the potential of exosomal miR‐500a‐3p as an potential modality for the prediction and treatment of GC with chemoresistance.

中文翻译：

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外泌体MiR-500a-3p通过负调节胃癌中的FBXW7促进顺铂耐药性和干性。

化学抗性一直是晚期胃癌（GC）治疗中的主要挑战。致癌性miRNA的外体转移在通过传递活性分子介导受体细胞化学抗性中起重要作用。在这项研究中，我们发现microRNA-500a-3p在顺铂（DDP）耐药的GC细胞（MGC803 / DDP和MKN45 / DDP）及其分泌的外泌体中比相应的亲代细胞中高表达。MGC803 / DDP衍生的外泌体通过靶向FBXW7在体外和体内通过miR-500a-3p的外泌体传递来增强MGC803受体细胞的DDP抗性和干性。但是，在MGC803细胞中重新引入FBXW7可以逆转miR-500a-3p介导的DDP耐药性以及茎特性。此外，GC患者血浆外泌体中miR-500a-3p的升高与DDP耐药相关，因此导致无进展的不良预后。我们的发现凸显了外泌体miR-500a-3p作为具有化学抗性的GC预测和治疗的潜在方式的潜力。