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Updated: Nov 12, 2025

A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in
Tiannan Zou1,2,3, Weibing Liu1, Zeyu Wang1,3
1Department of Orthopedic Surgery, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
Abstract:
Objective: Targeting cancer-specific messenger RNAs (mRNAs) may offer novel insights into therapeutic strategies in osteosarcoma. This study aimed to discover possible osteosarcoma-specific mRNA and probe its biological functions. Methods: Based on mRNA-seq data from the TARGET database, stromal and immune scores were estimated for each osteosarcoma sample via the ESTIMATE algorithm. Stromal and immune mRNAs were obtained via integration of differentially expressed mRNAs between high and low stromal / immune score groups. Among hub and prognostic mRNAs, C3AR1 mRNA was focused and its prognostic value was assessed. The associations between C3AR1 mRNA and immune cells were analyzed via the CIBERSORT algorithm. Its expression was verified in osteosarcoma tissues and cells by RT-qPCR and western blot. The functions of C3AR1 were investigated by a series of experiments. Results: Low stromal and immune scores were both indicative of unfavorable outcomes for osteosarcoma patients. Eighty-eight up-regulated and seven down-regulated stromal and immune mRNAs were identified. Among 30 hub mRNAs, low expression of C3AR1 mRNA indicated worse outcomes than its high expression. There was a lower mRNA expression of C3AR1 in metastatic than non-metastatic osteosarcoma. C3AR1 mRNA was closely correlated to various immune cells such as macrophages. C3AR1 was verified to be down-regulated in osteosarcoma tissues and cells. Its overexpression suppressed proliferation, migration and invasion and induced apoptosis in osteosarcoma cells. Conclusion: C3AR1 mRNA could be a promising therapeutic target for osteosarcoma, linked with prognosis and tumor microenvironment.
Insights
Osteosarcoma treatment may be improved by targeting C3AR1 messenger RNA (mRNA). Low C3AR1 mRNA levels correlate with poor prognosis and increased metastasis, suggesting C3AR1 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Targeting cancer-specific messenger RNAs (mRNAs) presents novel therapeutic strategies for osteosarcoma.
- Understanding the role of specific mRNAs in osteosarcoma progression and the tumor microenvironment is crucial.
Purpose of the Study:
- To identify osteosarcoma-specific mRNAs and investigate their biological functions.
- To evaluate the prognostic value of C3AR1 mRNA in osteosarcoma.
- To explore the association between C3AR1 mRNA and the tumor immune microenvironment.
Main Methods:
- Utilized mRNA sequencing data from the TARGET database to analyze gene expression.
- Employed ESTIMATE and CIBERSORT algorithms to assess stromal/immune scores and immune cell infiltration.
- Validated C3AR1 mRNA expression and function through RT-qPCR, western blot, and functional assays.
Main Results:
- Low stromal and immune scores were associated with unfavorable osteosarcoma patient outcomes.
- C3AR1 mRNA was found to be downregulated in osteosarcoma tissues and correlated with better prognosis.
- Overexpression of C3AR1 suppressed osteosarcoma cell proliferation, migration, invasion, and induced apoptosis.
Conclusions:
- C3AR1 mRNA is a potential prognostic biomarker for osteosarcoma.
- C3AR1 mRNA plays a significant role in regulating the tumor microenvironment and cancer cell behavior.
- C3AR1 mRNA represents a promising therapeutic target for osteosarcoma treatment.
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