Abstract

Exosomes from human umbilical cord mesenchymal stem cells (HUCMSCs) containing microRNAs (miRNAs) have been underscored as possible therapeutic options for cancers. Hence, our goal here was to investigate the relevance of miR-320a-containing exosomes from HUCMSCs to lung cancer. First, H1299 and H460 cells were co-cultured with the exosomes overexpressing miR-320a from HUCMSCs. The data displayed that HUCMSCs-secreted exosomes expressing miR-320a exerted anti-tumor effects in vitro and in vivo. Online analysis available at TargetScan database revealed that miR-320a bound to sex-determining region Y-box 4 (SOX4), and the luciferase reporter gene assay clarified this targeting relationship. Next, a β-catenin-specific agonist WAY-262611 was delivered into the H1299 and H460 cells to assess the effects of the Wnt/β-catenin pathway on lung cancer cellular processes. The results demonstrated that WAY-262611 potentiated lung cancer cell viability, invasion, and migration, but inhibited cell apoptosis. Altogether, exosomes carrying miR-320a from HUCMSCs might suppress lung cancer cell growth via the SOX4/Wnt/β-catenin axis, which highpoints the potency of exosomes expressing miR-320a as a possible therapeutic option for lung cancer treatment.

摘要

来自人脐带间充质干细胞 (HUCMSCs) 的含有 microRNA (miRNA) 的外泌体已被强调为癌症的可能治疗选择。因此，我们的目标是研究 HUCMSCs 中含有 miR-320a 的外泌体与肺癌的相关性。首先，H1299 和 H460 细胞与来自 HUCMSCs 的过表达 miR-320a 的外泌体共培养。数据显示，HUCMSCs分泌的表达miR-320a的外泌体在体外和体内发挥抗肿瘤作用. TargetScan 数据库提供的在线分析显示 miR-320a 与性别决定区 Y-box 4 (SOX4) 结合，荧光素酶报告基因分析阐明了这种靶向关系。接下来，将 β-catenin 特异性激动剂 WAY-262611 递送到 H1299 和 H460 细胞中，以评估 Wnt/β-catenin 途径对肺癌细胞过程的影响。结果表明，WAY-262611 增强了肺癌细胞的活力、侵袭和迁移，但抑制了细胞凋亡。总之，携带来自 HUCMSCs 的 miR-320a 的外泌体可能通过SOX4/Wnt/β-catenin 轴抑制肺癌细胞的生长，这突出了表达 miR-320a 的外泌体作为肺癌治疗的可能治疗选择的效力。