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Bone marrow mesenchymal stem cell-derived exosomal LINC00847 inhibits the proliferation, migration, and invasion of Ewing sarcoma.


ABSTRACT:

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 quantitative real time-polymerase chain reaction (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 ES.

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.

SUBMITTER: Huang L 

PROVIDER: S-EPMC9741936 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Bone marrow mesenchymal stem cell-derived exosomal LINC00847 inhibits the proliferation, migration, and invasion of Ewing sarcoma.

Huang Lu L   Xiong Jiachao J   Fu Jimin J   Zhou Zhenhai Z   Yu Honggui H   Xu Jiang J   Wu Liang L   Cao Kai K  

Journal of clinical and translational research 20221124 6


<h4>Background</h4>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.<h4>Aim</h4>This study aimed to investigate the role of exosomal lncRNAs from BMSCs in the pathogenesis of ES.<h4>Methods</h4>Bioinformatic analysis and  ...[more]

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