C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma

Tiannan Zou; Weibing Liu; Zeyu Wang; Jiayu Chen; Sheng Lu; Kun Huang; Weichao Li

doi:10.3389/fmed.2021.642615

C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma

Front Med (Lausanne). 2021 Mar 5:8:642615. doi: 10.3389/fmed.2021.642615. eCollection 2021.

Authors

Tiannan Zou^{1

2

3}, Weibing Liu¹, Zeyu Wang^{1

3}, Jiayu Chen^{1

3}, Sheng Lu^{1

2

3}, Kun Huang^{1

3}, Weichao Li^{1

2

3}

Affiliations

¹ Department of Orthopedic Surgery, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
² Faculty of Medical Science, Kunming University of Science and Technology, Kunming, China.
³ Yunnan Key Laboratory of Digital Orthopaedics, 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.

Keywords: C3AR1; mRNA; osteosarcoma; prognosis; therapeutic target; tumor immune microenvironment.