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Published on: June 16, 2023
Identification and validation of microRNAs and their targets expressed in osteosarcoma
Can Zhang1, Jun Wan1, Feng Long1
1Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Abstract:
Osteosarcoma (OS) is the most common type of bone cancer in children and adolescents, and has a poor prognosis. Previous studies have demonstrated that a number of microRNAs (miRNAs) were deregulated in OS, and that the expression of certain miRNAs was correlated with the stage of OS. Therefore, miRNAs may serve a role as a diagnostic and prognostic biomarker of OS. miRNA and mRNA integrated analysis of public expression profiles in the Gene Expression Omnibus database for OS was performed, and the regulated targets of miRNA in OS were predicted. Next, the regulatory network of miRNAs/genes was constructed and verified by reverse transcription-quantitative polymerase chain reaction in tissues and MG-63 cell lines. Two miRNA expression profiling studies and four eligible mRNA expression profiling studies were selected. Ten upregulated miRNAs, 5 downregulated miRNAs and 5 DGEs were identified in OS compared with normal tissues. hsa-miR-346 was inversely correlated with the target gene c-FLIP, which was consistent with the results of integrated analysis. In vitro, pre-miRNA-346 can downregulate the protein expression of c-FLIP, while not changing the mRNA level of c-FLIP. In the regulatory network, hsa-miR-346 and its target gene, c-FLIP, can be used as biomarkers for an earlier diagnosis of OS.
Insights
MicroRNAs (miRNAs) show altered expression in osteosarcoma (OS), a bone cancer. The study identified hsa-miR-346 as a potential diagnostic biomarker for OS by targeting c-FLIP.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is a prevalent bone cancer in children and adolescents with a poor prognosis.
- MicroRNAs (miRNAs) are implicated in OS development and progression, with deregulated expression linked to disease stage.
- miRNAs hold potential as diagnostic and prognostic biomarkers for OS.
Purpose of the Study:
- To identify dysregulated miRNAs and their mRNA targets in osteosarcoma (OS).
- To construct and validate a miRNA-mRNA regulatory network for OS.
- To evaluate the potential of specific miRNA-mRNA interactions as diagnostic biomarkers for OS.
Main Methods:
- Integrated analysis of public miRNA and mRNA expression profiles from the Gene Expression Omnibus (GEO) database for OS.
- Prediction of miRNA targets and construction of a miRNA-mRNA regulatory network.
- Validation of miRNA-mRNA interactions using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in OS tissues and cell lines.
Main Results:
- Ten upregulated and 5 downregulated miRNAs were identified in OS compared to normal tissues.
- hsa-miR-346 was found to be inversely correlated with its target gene, c-FLIP.
- In vitro experiments confirmed that pre-miRNA-346 downregulates c-FLIP protein expression without affecting mRNA levels.
Conclusions:
- The study identified key differentially expressed genes (DGEs) and miRNAs in osteosarcoma.
- The hsa-miR-346/c-FLIP axis represents a potential regulatory network in OS.
- hsa-miR-346 and c-FLIP show promise as biomarkers for early diagnosis of osteosarcoma.
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