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Role of miRNA-542-5p in the tumorigenesis of osteosarcoma.

ABSTRACT: Osteosarcoma, one of the most common malignant bone tumors, is characterized by a high rate of metastasis, and the survival rate of patients with metastatic osteosarcoma is poor. Previous studies have reported that miRNAs often regulate the occurrence and development of various tumors. In this work, we identified miRNA-542-5p as a critical miRNA in osteosarcoma by overlapping three Gene Expression Omnibus datasets, and then evaluated miRNA-542-5p expression profiles using Gene Expression Omnibus and Sarcoma-microRNA Expression Database. We used MISIM to investigate miRNAs correlated with miR-542 and identified potential target genes of miRNA-542-5p using miRWalk. Functional and pathway enrichment analyses were performed using The Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction was performed using Search Tool for the Retrieval of Interacting Genes and Cytoscape. We report that the relative level of miRNA-542-5p was significantly higher in osteosarcoma than in healthy bone. Expressions of hsa-miR-330 and hsa-miR-1202 were found to be strongly correlated with that of miR-542-5p. Furthermore, we identified a total of 514 down-regulated genes as possible targets of miR-542-5p. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that the putative target genes of miR-542-5p were most enriched in the cell-cycle process. The differentially expressed genes CDCA5, PARP12 and HSPD1 were found to be hub genes in protein-protein interaction networks. Finally, transfection of the osteosarcoma cell line U2OS with miR-542-5p mimics or inhibitor revealed that miR-542-5p can promote cell proliferation. In conclusion, our results suggest that miR-542-5p may promote osteosarcoma proliferation; thus, this miRNA may have potential as a biomarker for diagnosis and prognosis.

SUBMITTER: Zhu T

PROVIDER: S-EPMC7137799 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Role of miRNA-542-5p in the tumorigenesis of osteosarcoma.

Zhu Tengjiao T Fan Daoyang D Ye Kaifeng K Liu Bingchuan B Cui Zhiyong Z Liu Zhongjun Z Tian Yun Y

FEBS open bio 20200318 4

Osteosarcoma, one of the most common malignant bone tumors, is characterized by a high rate of metastasis, and the survival rate of patients with metastatic osteosarcoma is poor. Previous studies have reported that miRNAs often regulate the occurrence and development of various tumors. In this work, we identified miRNA-542-5p as a critical miRNA in osteosarcoma by overlapping three Gene Expression Omnibus datasets, and then evaluated miRNA-542-5p expression profiles using Gene Expression Omnibus ...[more]

PMID: 32105410

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Project description:Osteosarcoma (OS) is the most common pediatric primary bone tumor, with high malignancy rates and a poor prognosis following metastasis. At present, the role of microRNA (miR)?542?3p in OS remains to be elucidated. The purpose of the present study was to investigate the expression level of miR?542?3p in OS, and its potential molecular mechanisms, via a bioinformatics analysis. First, the expression of miR?542?3p in OS based on the continuous variables of the Gene Expression Omnibus database and PubMed was studied. Subsequently, the potential target genes of miR?542?3p were predicted using gene expression profiles and bioinformatics software. On the basis of the Database for Annotation, Visualization and Integrated Discovery, version 6.8, a study of gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway knowledge base was conducted to explore the biological value of miR?542?3p in OS. Finally, the protein?protein interaction (PPI) network was completed using the STRING database. The expression of miR?542?3p in OS was revealed to be significantly higher compared with that in normal tissue. In total, 1,036 target genes of miR?542?3p were obtained. The results of the GO enrichment analysis revealed that the significant terms were 'bone development', 'cell cycle arrest' and 'intracellular signal transduction'. The results of the KEGG analysis revealed the highlighted pathways that were targeted to miR?542?3p, including the sphingolipid signaling pathway (P=3.91x10?5), the phosphoinositide 3?kinase (PI3K)?AKT serine/threonine kinase (AKT) signaling pathway (P=3.17x10?5) and the insulin signaling pathway (P=1.04x10?5). The PPI network revealed eight hub genes: Ubiquitin?60S ribosomal protein L40, Ras?related C3 botulinum toxin substrate, mitogen?activated protein kinase 1, epidermal growth factor receptor, cystic fibrosis transmembrane conductance regulator, PI3K regulatory subunit 1, AKT1, and actin?related protein 2/3 complex subunit 1A, which may be the key target genes of miR?542?3p in OS. Taken together, these results have demonstrated that miR?542?3p was overexpressed in OS. The potential target genes and biological functions of miR?542?3p may provide novel insights into the differentially expressed genes that are involved in OS.

Project description:Osteosarcoma (OS) is the most common pediatric malignant bone tumor, and occurrence of pulmonary metastasis generally causes a rapid and fatal outcome. Here we aimed to provide clues for exploring the mechanism of tumorigenesis and pulmonary metastasis for OS by comprehensive analysis of microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA expression in primary OS and OS pulmonary metastasis. In this study, deep sequencing with samples from primary OS (n?=?3), pulmonary metastatic OS (n?=?3), and normal controls (n?=?3) was conducted and differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs), and mRNAs (DEmRNAs) between primary OS and normal controls as well as pulmonary metastatic and primary OS were identified. A total of 65 DEmiRNAs, 233 DElncRNAs, and 1405 DEmRNAs were obtained between primary OS and normal controls; 48 DEmiRNAs, 50 DElncRNAs, and 307 DEmRNAs were obtained between pulmonary metastatic and primary OS. Then, the target DEmRNAs and DElncRNAs regulated by the same DEmiRNAs were searched and the OS tumorigenesis-related and OS pulmonary metastasis-related competing endogenous RNA (ceRNA) networks were constructed, respectively. Based on these ceRNA networks and Venn diagram analysis, we obtained 3 DEmiRNAs, 15 DElncRNAs, and 100 DEmRNAs, and eight target pairs including miR-223-5p/(CLSTN2, AC009951.1, LINC01705, AC090673.1), miR-378b/(ALX4, IGSF3, SULF1), and miR-323b-3p/TGFBR3 were involved in both tumorigenesis and pulmonary metastasis of OS. The TGF-? superfamily co-receptor TGFBR3, which is regulated by miR-323b-3p, acts as a tumor suppressor in OS tumorigenesis and acts as a tumor promoter in pulmonary metastatic OS via activation of the epithelial-mesenchymal transition (EMT) program.In conclusion, the OS transcriptome (miRNA, lncRNA, and mRNA) is dynamically regulated. These analyses might provide new clues to uncover the molecular mechanisms and signaling networks that contribute to OS progression, toward patient-tailored and novel-targeted treatments.

Dataset Information

Role of miRNA-542-5p in the tumorigenesis of osteosarcoma.

Publications

Role of miRNA-542-5p in the tumorigenesis of osteosarcoma.

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