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人脐带来源间充质干细胞分泌的外泌体通过 PTENP1/miR-10a-5p/PTEN 通路抑制神经胶质瘤细胞的进展。

hUC-MSCs secreted exosomes inhibit the glioma cell progression through PTENP1/miR-10a-5p/PTEN pathway.

机构信息

Ningxia Medical University, Yinchuan, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Nov;23(22):10013-10023. doi: 10.26355/eurrev_201911_19568.

DOI:10.26355/eurrev_201911_19568
PMID:31799671
Abstract

OBJECTIVE

The mesenchymal stem cells (MSCs) have been widely studied for their anti-tumor property, due to the characteristic of homing towards tumor sites and immunosuppression. Nevertheless, the underlying molecular mechanisms that link MSCs to the targeted tumor cells, such as glioma, are not clear.

MATERIALS AND METHODS

Here, we examined the inhibitory properties and new molecular mechanisms of the human umbilical cord (hUC-MSCs) derived exosomes on the human glioma U87 cells using a co-culture system in vitro. The cell counting kit-8 (CCK-8) assay was performed to measure the anti-tumor activity of hUC-MSCs derived exosomes. The cell apoptosis was assessed by flow cytometry and the immunoblotting assay was applied in order to assess the associated proteins level. The data revealed that hUC-MSCs derived exosomes could repress cell proliferation and induce cell apoptosis.

RESULTS

Mechanistically, we identified that lncRNA PTENP1 could be packaged into exosome from hUC-MSCs, transferred to U87 cells, and then stabilized PTEN by binding miR-10a-5p competitively.

CONCLUSIONS

Therefore, our data suggested that the exosomes from hUC-MSCs possess a higher anti-tumor capacity, at least partially, via regulating miR-10a-5p/PTEN signaling, which thereby may represent a possible target for early diagnosis and treatment of glioma clinically.

摘要

目的

间充质干细胞 (MSCs) 因其向肿瘤部位归巢和免疫抑制的特性而被广泛研究用于抗肿瘤。然而,将 MSCs 与靶向肿瘤细胞(如神经胶质瘤)联系起来的潜在分子机制尚不清楚。

材料和方法

在这里,我们使用体外共培养系统研究了人脐带(hUC-MSCs)来源的外泌体对人神经胶质瘤 U87 细胞的抑制特性和新的分子机制。使用细胞计数试剂盒-8(CCK-8)测定法测量 hUC-MSCs 衍生的外泌体的抗肿瘤活性。通过流式细胞术评估细胞凋亡,并用免疫印迹法评估相关蛋白水平。数据显示,hUC-MSCs 衍生的外泌体可以抑制细胞增殖并诱导细胞凋亡。

结果

从机制上讲,我们鉴定出 lncRNA PTENP1 可以从 hUC-MSCs 包装到外泌体中,然后转移到 U87 细胞中,并通过竞争性结合 miR-10a-5p 稳定 PTEN。

结论

因此,我们的数据表明,hUC-MSCs 的外泌体通过调节 miR-10a-5p/PTEN 信号至少部分地具有更高的抗肿瘤能力,这可能代表了神经胶质瘤临床早期诊断和治疗的一个潜在靶点。

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