To Explore the Mechanism of the GRM4 Gene in Osteosarcoma by RNA Sequencing and Bioinformatics Approach
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Updated: Feb 15, 2026

A Bioinformatics Pipeline for Investigating Molecular Evolution and Gene Expression using RNA-seq
Published on: May 28, 2021
Yunguo Pang1,2, Jinmin Zhao2,3, Mitra Fowdur1,2
1Division of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).
Abstract:
BACKGROUND Glutamate metabotropic receptor 4 (GRM4) has been correlated with the pathogenesis of osteosarcoma. The objective of this study was to explore the underlying molecular mechanism of GRM4 in osteosarcoma. MATERIAL AND METHODS The expression levels of GRM4 in four human osteosarcoma cell lines and hFOB1.19 cells were examined by real-time quantitative PCR (RT-qPCR). The U2OS cells of the highest GRM4 expression were transfected with lentivirus-mediated small interfering RNA (siRNA). The differentially expressed genes (DEGs) after GRM4 gene silencing were screened through RNA sequencing, and analyzed by bioinformatics. Additionally, the transcription factors (TFs) targeting GRM4 were predicted and the downstream protein-protein interaction (PPI) network was constructed using the bioinformatics approach. RESULTS A total of 51 significant DEGs were obtained, including 14 upregulated and 37 downregulated DEGs. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs indicated that four significant enrichment pathways were obtained. A total of six TFs that could be involved in the transcriptional regulation of GRM4 were detected. The results showed that 182 genes in the PPI network were significantly enriched in 14 pathways. The chemokines and chemokine receptors were found to be significantly enriched in three pathways. CONCLUSIONS The DEGs in the four significant enrichment pathways might participate in the development and progression of osteosarcoma through GRM4. The results revealed that EGR1 and CTCF are probably involved in the transcriptional regulation of GRM4, which participates in the progress of osteosarcoma by interacting with chemokines and their receptors.
Insights
Glutamate metabotropic receptor 4 (GRM4) plays a role in osteosarcoma. Silencing GRM4 identified key genes and pathways involved in osteosarcoma development, suggesting EGR1 and CTCF as regulatory factors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glutamate metabotropic receptor 4 (GRM4) is implicated in osteosarcoma pathogenesis.
- Understanding GRM4's molecular mechanisms is crucial for osteosarcoma research.
Purpose of the Study:
- To investigate the molecular mechanisms of GRM4 in osteosarcoma.
- To identify genes and pathways regulated by GRM4 in osteosarcoma cells.
Main Methods:
- Real-time quantitative PCR (RT-qPCR) to assess GRM4 expression.
- RNA sequencing and bioinformatics analysis for differentially expressed genes (DEGs) after GRM4 silencing.
- Prediction of transcription factors (TFs) and construction of protein-protein interaction (PPI) networks.
Main Results:
- 51 significant DEGs were identified, with 14 upregulated and 37 downregulated.
- KEGG pathway analysis revealed four significant enrichment pathways.
- Six TFs potentially regulating GRM4 were detected; EGR1 and CTCF were highlighted.
- A PPI network identified 182 genes enriched in 14 pathways, with chemokines and receptors in three pathways.
Conclusions:
- DEGs in identified pathways likely contribute to osteosarcoma development via GRM4.
- EGR1 and CTCF are potential regulators of GRM4 in osteosarcoma progression.
- GRM4's role in osteosarcoma involves interactions with chemokines and their receptors.
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