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Published on: June 16, 2023
Microarray Expression Profile and Functional Analysis of Circular RNAs in Osteosarcoma
Background/Aims:
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. However, the molecular mechanisms regulating osteosarcoma tumorigenesis and progression are still poorly understood. Circular RNAs (circRNAs) have been identified as microRNA sponges and are involved in many important biological processes. This study aims to investigate the global changes in the expression pattern of circRNAs in osteosarcoma and provide a comprehensive understanding of differentially expressed circRNAs.
Methods:
Microarray based circRNA expression was determined in osteosarcoma cell lines and compared with hFOB1.19, which was used as the normal control. We confirmed the microarray data by real time-qPCR in both osteosarcoma cell lines and tissues. The circRNA/microRNA/mRNA interaction network was predicted using bioinformatics. Gene Ontology analysis and 4 annotation tools for pathway analysis (KEGG, Biocarta, PANTHER and Reactome) were used to predict the functions of differentially expressed circRNAs.
Results:
We revealed a number of differentially expressed circRNAs and 12 of them were confirmed, which suggests a potential role of circRNAs in OS. Among these differentially expressed circRNAs, hsa_circRNA_103801 was up-regulated in both osteosarcoma cell lines and tissues, while hsa_circRNA_104980 was down-regulated. The most likely potential target miRNAs for hsa_circRNA_103801 include hsa-miR-370-3p, hsa-miR-338-3p and hsa-miR-877-3p, while the most potential target miRNAs of hsa_circRNA_104980 consist of hsa-miR-1298-3p and hsa-miR-660-3p. Functional analysis found that hsa_circRNA_103801 was involved in pathways in cancer, such as the HIF-1, VEGF and angiogenesis pathway, the Rap1 signaling pathway and the PI3K-Akt signaling pathway, while hsa_circRNA_104980 was related to some pathways such as the tight junction pathway.
Conclusions:
This study has identified the comprehensive expression profile of circRNAs in osteosarcoma for the first time. And the ceRNA network prediction and bioinformatics functional analysis could provide a comprehensive understanding of hsa_circRNA_103801 and hsa_circRNA_104980, which may be involved in the initiation and progression of osteosarcoma. The present study indicates that circRNAs may play important roles in osteosarcoma and thus serve as biomarkers of osteosarcoma diagnosis and treatment.
Insights
This study identified differentially expressed circular RNAs (circRNAs) in osteosarcoma, revealing potential roles for hsa_circRNA_103801 and hsa_circRNA_104980 in tumor development. These findings suggest circRNAs could be novel biomarkers for osteosarcoma diagnosis and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is a primary bone cancer in children and adolescents with poorly understood molecular mechanisms.
- Circular RNAs (circRNAs) are emerging regulators of gene expression, acting as microRNA sponges.
- Investigating circRNA expression profiles in OS is crucial for understanding tumorigenesis.
Purpose of the Study:
- To profile global circRNA expression in osteosarcoma.
- To identify differentially expressed circRNAs in OS.
- To elucidate the functional roles and interactions of key circRNAs in OS progression.
Main Methods:
- circRNA expression profiling using microarray analysis in OS cell lines and normal controls.
- Validation of differentially expressed circRNAs via real-time quantitative PCR (qPCR) in OS cell lines and tissues.
- Bioinformatic prediction of circRNA/microRNA/mRNA interactions and functional pathway analysis (GO, KEGG, Biocarta, PANTHER, Reactome).
Main Results:
- A distinct circRNA expression profile was identified in osteosarcoma.
- Twelve differentially expressed circRNAs were confirmed, including up-regulated hsa_circRNA_103801 and down-regulated hsa_circRNA_104980.
- Functional analysis linked hsa_circRNA_103801 to cancer-related pathways (e.g., HIF-1, VEGF, angiogenesis, PI3K-Akt) and hsa_circRNA_104980 to the tight junction pathway.
Conclusions:
- This study provides the first comprehensive circRNA expression profile in osteosarcoma.
- Predicted ceRNA networks highlight hsa_circRNA_103801 and hsa_circRNA_104980 as potentially significant in OS initiation and progression.
- circRNAs represent promising novel biomarkers for osteosarcoma diagnosis and therapeutic strategies.
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