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人骨髓间充质干细胞来源的miR-1913通过外泌体转移靶向NRSN2抑制骨肉瘤进展。

The exosomal transfer of human bone marrow mesenchymal stem cell-derived miR-1913 inhibits osteosarcoma progression by targeting NRSN2.

作者信息

Zhou Jihui, Xu Lili, Yang Peng, Lu Yao, Lin Shibang, Yuan Guanghai

机构信息

Department of Traumatic Orthopedics, Maoming People's Hospital Maoming, Guangdong Province, China.

Department of Center Vaccination Clinic, Fuchunjiang Community Health Service Center of Changjiang Road West Coast New District of Qingdao, Qingdao, Shandong Province, China.

出版信息

Am J Transl Res. 2021 Sep 15;13(9):10178-10192. eCollection 2021.

Abstract

OBJECTIVE

Osteosarcoma is a malignant bone tumor consisting of mesenchymal cells. This study aimed to investigate the inhibitory effects of human bone marrow mesenchymal stem cell (hBMSC)-derived miR-1913 on osteosarcoma.

METHODS

Cell viability was determined using CCK8 and colony formation assays. The cell migration and invasion abilities were assessed using wound healing and transwell assays. RT-qPCR and western blot were used to measure the miR-1913, Neurensin-2 (NRSN2), N-cadherin, and E-cadherin expression levels. Dual luciferase reporter assays were conducted to identify the target relationship between miR-1913 and NRSN2. The exosomes were extracted and identified using TEM and NTA assays.

RESULTS

In the osteosarcoma tumor tissues and cell lines, the NRSN2 expressions were up-regulated, which correlated with a poor osteosarcoma prognosis. MiR-1913 inhibited the cell viability, proliferation, migration, and invasion by negatively targeting NRSN2. Furthermore, the hBMSC-derived exosomes delivered miR-1913 to inhibit the NRSN2 expression in the osteosarcoma cells.

CONCLUSION

The inhibitory role of hBMSC-derived miR-1913 on osteosarcoma progression was achieved by targeting NRSN2, indicating the potential therapeutic value of hBMSC-derived miR-1913.

摘要

目的

骨肉瘤是一种由间充质细胞构成的恶性骨肿瘤。本研究旨在探究人骨髓间充质干细胞(hBMSC)来源的miR-1913对骨肉瘤的抑制作用。

方法

采用CCK8和集落形成试验测定细胞活力。使用伤口愈合试验和Transwell试验评估细胞迁移和侵袭能力。采用RT-qPCR和蛋白质印迹法检测miR-1913、神经连接蛋白2(NRSN2)、N-钙黏蛋白和E-钙黏蛋白的表达水平。进行双荧光素酶报告基因试验以确定miR-1913与NRSN2之间的靶向关系。采用透射电子显微镜(TEM)和纳米颗粒跟踪分析(NTA)试验提取并鉴定外泌体。

结果

在骨肉瘤肿瘤组织和细胞系中,NRSN2表达上调,这与骨肉瘤预后不良相关。MiR-1913通过负向靶向NRSN2抑制细胞活力、增殖、迁移和侵袭。此外,hBMSC来源的外泌体递送miR-1913以抑制骨肉瘤细胞中NRSN2的表达。

结论

hBMSC来源的miR-1913通过靶向NRSN2实现对骨肉瘤进展的抑制作用,表明hBMSC来源的miR-1913具有潜在的治疗价值。

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