Expression of miR‑542‑3p in osteosarcoma with miRNA microarray data, and its potential signaling pathways

Abstract

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=3.91×10−5), the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (AKT) signaling pathway (P=3.17×10−5) and the insulin signaling pathway (P=1.04×10−5). 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.

miR-542-3p Attenuates Bone Loss and Marrow Adiposity Following Methotrexate Treatment by Targeting sFRP-1 and Smurf2

“…Our bioinformatics analyses of key target genes revealed that alanine, aspartate and glutamate metabolism and GABAergic synapse were significant KEGG pathways and in total, eight significantly enriched GO terms were identified, which might indicate the potential molecular mechanisms of miR-542-3p upon MTX therapy. Inconsistent with our findings, previous studies have shown that miR-542-3p was significantly increased in osteosarcoma tissue, and its bioinformatics analyses revealed that the sphingolipid signalling pathway ( p = 3.91 × 10 −5 ) and bone development were the most highlighted pathway and GO term, respectively [ 30 ]. These investigations demonstrated that the target genes and biological functions of miR-542-3p may vary with different pathological conditions.…”

“…Previous evidence showed that Wnt signalling and TGF-β signalling are the highlighted signalling pathways that can be affected by miR-542-3p [ 30 , 31 ]. Consistently, sFPR-1 and Smurf2, two direct targets identified in the current study, are known as antagonists for Wnt signalling and TGF-β signalling, respectively.…”

Research advances in molecular mechanisms underlying the pathogenesis of cystic fibrosis: From technical improvement to clinical applications (Review)

“…Non-coding RNAs (ncRNAs) in CF. Although CF is monogenic, the phenotypes of patients with CF are heterogeneous, which may be attributed to multiple regulators that contribute to CF pathogenesis (53) (53,(57)(58)(59). The inhibition of miR-145 through peptide nucleic acids was reported to promote the expression of CFTR, as miR-145 binds to the 3'-untranslated region (3'UTR) of the CFTR gene (57).…”