Abstract
Background Osteosarcoma is a malignant bone tumor composed of mesenchymal cells producing osteoid and immature bone. This study is aimed at developing novel potential prognostic biomarkers and constructing a miRNA-mRNA network for progression in osteosarcoma. Method GSE70367 and GSE70414 were obtained in the Gene Expression Omnibus (GEO) database. GEO software and the GEO2R calculation method were used to analyze two gene profiles. The coexpression of differentially expressed miRNAs (DEMs) and genes (DEGs) was identified and searched for in the FunRich database for pathway and ontology analysis. Cytoscape was utilized to construct the mRNA-miRNA network. Survival analysis of identified miRNAs and mRNAs was performed by utilizing the Kaplan-Meier Plotter. Besides, expression levels of DEMs and target mRNAs were verified by performing quantitative real-time PCR (qRT-PCR) and Western blot (WB). Results Six differentially expressed microRNAs (DEMs) were identified, and 8 target genes were selected after screening. By using the KM Plotter software, miRNA-124 and ARHGEF3 were obviously associated with the overall survival of patients with osteosarcoma. Furthermore, ARHGEF3 was found downregulated in osteosarcoma cells by performing qRT-PCR and WB experiments. Results also showed that downregulated ARHGEF3 may associate with invasion, metastasis, and proliferation. Conclusions By using microarray and bioinformatics analysis, DEMs were selected, and a complete miRNA-mRNA network was constructed. ARHGEF3 may act as a therapeutic and prognostic target of osteosarcoma.
Highlights
Osteosarcoma is a malignant bone tumor composed of mesenchymal cells producing osteoid and immature bone
We identified differentially expressed genes and microRNAs by analyzing 1 osteosarcoma mRNA microarray dataset and 1 microRNA dataset
GSE70367, including 5 osteosarcoma cell lines and 1 human mesenchymal stem cell line.. miRNA expression profiling research of these cell lines was conducted on an Affymetrix Multispecies miRNA-3 Array (GPL16384)
Summary
Osteosarcoma is a malignant bone tumor composed of mesenchymal cells producing osteoid and immature bone. This study is aimed at developing novel potential prognostic biomarkers and constructing a miRNA-mRNA network for progression in osteosarcoma. The coexpression of differentially expressed miRNAs (DEMs) and genes (DEGs) was identified and searched for in the FunRich database for pathway and ontology analysis. Survival analysis of identified miRNAs and mRNAs was performed by utilizing the Kaplan-Meier Plotter. Six differentially expressed microRNAs (DEMs) were identified, and 8 target genes were selected after screening. By using the KM Plotter software, miRNA-124 and ARHGEF3 were obviously associated with the overall survival of patients with osteosarcoma. Due to the lack of effective tumor early diagnostic markers, despite the rapid development of surgery, chemotherapy, radiotherapy, and other treatment methods, the long-term survival rate of patients with metastatic diseases remains at 25-30% [2]. It is urgent to have a deep understanding of its basic biology to determine its prognostic biomarkers and therapeutic targets [4]
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