Integrated analysis of lncRNA-associated ceRNA network identified potential regulatory interactions in osteosarcoma

Abstract

This study aimed to identify potential therapeutic targets in osteosarcoma (OS) through the network analysis of competing endogenous RNAs (ceRNAs). The differentially expressed miRNAs (DEMIs) and mRNAs (DEMs) were identified between OS cell lines and human mesenchymal stem cells (hMSCs) from the data deposited under GSE70415 using limma package. Functional analysis of DEMs was performed using DAVID and clusterProfiler to identify significantly enriched Gene Ontology biological processes and KEGG pathways, respectively. The DEMI-DEM interaction network was constructed using Cytoscape. LncRNA–miRNA interactions were predicted using starBase database. The ceRNA regulatory network was constructed by integrating mRNAs, miRNAs, and lncRNAs, and functional enrichment analysis was performed for the genes involved. The analysis revealed a total of 326 DEMs and 54 DEMIs between OS cells and hMSCs. We identified several novel therapeutic targets involved in the progression and metastasis of OS, such as CBX7, RAD9A, SNHG7 and miR-34a-5p. The miRNA, miR-543 (target gene: CBX7) was found to be associated with the pathway Mucin type O-glycan biosynthesis. Using the ceRNA network, we established the following regulatory interactions: NEAT1/miR-543/CBX7, SNHG7/miR-34a-5p/RAD9A, and XIST/miR-34a-5p/RAD9A. CBX7, RAD9A, lncRNA SNHG7, miR-543, and miR-34a-5p may be explored as novel therapeutic targets for treatment of OS.

Keywords
Osteosarcoma; differentially expression mRNA; differentially expression miRNA; competing endogenous RNAs network; lncRNA