Lu Huang†, Jiachao Xiong†, Jimin Fu†, Zhenhai Zhou, Honggui Yu, Jiang Xu, Liang Wu, Kai Cao*
Huang et al. J Clin Transl Res 2022; 8(6):15
Published online: November 24, 2022
Background: Ewing sarcoma (ES) is one of the most lethal primary bone tumors with a poor survival rate. Current evidence suggests that extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) loaded with abundant biological functional lncRNAs confer therapeutic benefits against the development of various tumors.
Aim: This study aimed to investigate the role of exosomal lncRNAs from BMSCs in the pathogenesis of ES.
Methods: Bioinformatic analysis and qRT-PCR experiments were used to detect the expression level of LINC00847 in ES tissues and cells. Cell biology experiments examined the effect of in vitro proliferation, migration, and invasion abilities and the biological function of BMSCs-derived LINC00847. Finally, we constructed a LINC00847-associated competitive endogenous RNA (ceRNA) network by in silico methods. Gene Set Enrichment Analysis (GSEA) was conducted to reveal the potential molecular mechanism of LINC00847.
Results: We found that LINC00847 was markedly downregulated in ES. Overexpression of LINC00847 inhibited ES cell proliferation, migration, and invasion. Furthermore, BMSCs-derived EVs inhibited the proliferation, migration, and invasion of ES cells by delivering LINC00847. We constructed a LINC00847 related-ceRNA network contains five miRNAs (miR-18a-5p, miR-18b-5p, miR-181a-5p, miR-181c-5p, and miR-485-3p) and four mRNAs (GFPT1, HIF1A, NEDD9, and NOTCH2).
Conclusions: Overall, this study found that BMSCs-EVs-derived exosomal LINC00847 inhibited ES cell proliferation, migration, and invasion. The ceRNA regulatory mechanism of LINC00847 may participate in the pathogenesis of the malignant phenotype of Ewing sarcoma.
Relevance for patients: These findings suggest that BMSCs-derived exosomal lncRNAs may be used for the personalized treatment of tumors, providing a novel theoretical framework for treating ES.
†These authors contributed equally
1. The Maternal and Children Health Hospital of Jiangxi Province, 318 Bayi Avenue, Nanchang, Jiangxi Province, 330006, China
2. The Orthopedics Hospital, The First Affiliated Hospital of Nanchang University, 1519 Dongyue Avenue, Nanchang County, Nanchang, Jiangxi Province, 330200, Chin
The Orthopedics Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330200, PR China.
Department of Pharmaceutics, Utrecht University, the Netherlands
Department of Pharmaceutics, Jiaxing University Medical College, Zhejiang, China
Epub ahead of print (2.2 MB)
Supplementary table 1 (19.7 KB)
Supplementary data (324.2 KB)