文章：

人骨髓基质细胞分泌含有microRNA -375的外泌体调控胶质瘤的进展

Human marrow stromal cells secrete microRNA-375-containing exosomes to regulate glioma progression 

原文发布日期：2019-02-07 

英文摘要：

It is well established that human marrow stromal cells (hMSCs) can directly migrate towards tumor microenvironments associated with tumor formation and intracellular communication. Gene regulatory networks in tumors may be targeted by microRNAs (miRNAs), especially those derived in exosomes from hMSCs. However, the potential functional roles of hMSCs in glioma cell growth still remain controversial. Therefore, this study aimed at exploring the regulatory mechanisms of hMSC exosomal microRNA-375 (miR-375) in glioma. Microarray analysis was used to initially screen out glioma-related genes. The interaction between miR-375 and solute carrier family 31 member 1 (SLC31A1) was confirmed by dual-luciferase reporter gene assay. miR-375 and SLC31A1 expression in glioma cells were determined. Glioma cells were initially exposed to exosomes derived from hMSCs treated with miR-375. Subsequently, the rates of proliferation, migration, invasion and apoptosis were determined in glioma cells using in vitro assays. The effects of exosomal miR-375 from hMSCs on tumor growth in vivo were also measured using xenograft tumor in nude mice. We found that miR-375 and SLC31A1 showed significantly lower and higher expression of glioma cells respectively. Additionally, restored miR-375 expression resulted in suppressed cell proliferation, migration and invasion, and increased apoptosis by targeting SLC31A1. Next, in vitro experiments demonstrated that hMSC-derived exosomes overexpressing miR-375 promoted apoptosis while suppressing proliferation, migration and invasion. Furthermore, in vivo experiments confirmed the negative regulatory effects of hMSC-derived exosomes with overexpressed miR-375. We conclude that exosomal miR-375 from hMSCs inhibits glioma cell progression through SLC31A1 suppression, and ultimately serves as a potential target in the treatment of gliomas. 

摘要翻译： 

已有明确研究表明，人骨髓基质细胞（hMSCs）能够直接迁移至肿瘤微环境，参与肿瘤形成与细胞间通讯。肿瘤中的基因调控网络可能受到microRNAs（miRNAs）的靶向调控，尤其是源自hMSCs外泌体中的miRNAs。然而，hMSCs在胶质瘤细胞生长中的潜在功能作用仍存在争议。因此，本研究旨在探讨hMSCs外泌体源性microRNA-375（miR-375）在胶质瘤中的调控机制。我们采用微阵列分析初步筛选胶质瘤相关基因，并通过双荧光素酶报告基因实验验证miR-375与溶质载体家族31成员1（SLC31A1）的相互作用。检测胶质瘤细胞中miR-375和SLC31A1的表达水平后，将胶质瘤细胞与经miR-375处理的hMSCs来源外泌体共培养，随后通过体外实验测定细胞增殖、迁移、侵袭和凋亡率。同时采用裸鼠异种移植瘤模型评估hMSCs外泌体miR-375对体内肿瘤生长的影响。研究发现：miR-375在胶质瘤细胞中表达显著降低，而SLC31A1表达显著升高；恢复miR-375表达可通过靶向SLC31A1抑制细胞增殖、迁移和侵袭并促进凋亡。体外实验表明，过表达miR-375的hMSCs来源外泌体能促进细胞凋亡，同时抑制增殖、迁移和侵袭。体内实验进一步证实过表达miR-375的hMSCs外泌体具有负向调控作用。我们得出结论：hMSCs来源的外泌体miR-375通过抑制SLC31A1阻遏胶质瘤细胞进展，最终可作为胶质瘤治疗的潜在靶点。

原文链接：

Human marrow stromal cells secrete microRNA-375-containing exosomes to regulate glioma progression