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A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
Screening for MicroRNA combination with engineered exosomes as a new tool against osteosarcoma in elderly patients
Jiyu Han1,2, Zitong Zhao2, Yanhong Wang1,2
1School of Medicine, Department of Orthopedics, Tongji Hospital, Tongji University, Shanghai, China.
Abstract:
The most common primary malignant bone sarcoma is Osteogenic sarcoma (OS) which has a bimodal age distribution. Unfortunately, the treatment of OS was less effective for elderly patients than for younger ones. The study aimed to explore a new microRNA (miRNA) which can bind to combining engineered exosomes for treatment of older OS patients. Based on GSE65071 and miRNet 2.0, two up-regulated miRNAs (miR-328, miR-107) and seven down-regulated miRNAs (miR-133b, miR-206, miR-1-3p, miR-133a, miR-449a, miR-181daysay, miR-134) were selected. Next, we used FunRich software to predict the up-stream transcription factors (TFs) of differentially expressed miRNAs (DE-miRNAs). By comparing target genes predicted from DE-miRNAs with differentially expressed genes, we identified 12 down-regulated and 310 up-regulated mRNAs. For KEGG analysis, the most enriched KEGG pathway was Cell cycle, Spliceosome, and Protein digestion and absorption. By using protein-protein interactions network, topological analysis algorithm and GEPIA database, miR-449a /CCNB1 axis was identified. Experiments in vitro were conducted to confirm the results too. MiRNA-449a is down-regulated in osteosarcoma and suppresses cell proliferation by targeting CCNB1. Our findings not only reveal a novel mechanism of miR-449a /CCNB1 in OS but also had laid the groundwork for further investigation and analysis in the field of exosome engineering.
Insights
This study identifies miR-449a as a key microRNA (miRNA) that suppresses osteosarcoma (OS) cell growth by targeting CCNB1. This discovery offers a potential new therapeutic strategy for elderly OS patients using engineered exosomes.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Osteosarcoma (OS) is the most common primary malignant bone sarcoma with less effective treatments for elderly patients.
- Engineered exosomes offer a potential delivery vehicle for novel therapeutic agents in OS treatment.
- Understanding microRNA (miRNA) dysregulation in OS is crucial for developing targeted therapies.
Purpose of the Study:
- To identify novel microRNAs (miRNAs) for the potential treatment of elderly osteosarcoma (OS) patients.
- To explore the therapeutic potential of engineered exosomes carrying specific miRNAs for OS.
- To elucidate the molecular mechanisms underlying miRNA regulation in osteosarcoma.
Main Methods:
- Bioinformatic analysis of gene expression datasets (GSE65071) and miRNA databases (miRNet 2.0).
- Identification of differentially expressed miRNAs (DE-miRNAs) and their upstream transcription factors (TFs).
- KEGG pathway analysis, protein-protein interaction network analysis, and *in vitro* experiments to validate the miR-449a/CCNB1 axis.
Main Results:
- Two up-regulated and seven down-regulated miRNAs were identified in osteosarcoma.
- The miR-449a/CCNB1 axis was identified as a significant pathway in OS.
- MiRNA-449a was found to be down-regulated in osteosarcoma and suppresses cell proliferation by targeting CCNB1.
Conclusions:
- MiR-449a plays a tumor-suppressive role in osteosarcoma by targeting CCNB1.
- The miR-449a/CCNB1 axis represents a novel mechanism in OS pathogenesis.
- This research lays the foundation for developing exosome-based miRNA therapies for elderly OS patients.
