Identification of Potential Genomic Alterations and the circRNA-miRNA-mRNA Regulatory Network in Primary and Recurrent Synovial Sarcomas

Abstract

Introduction: Synovial sarcoma (SS) is one of the most invasive soft tissue sarcomas, prone to recurrence and metastasis, and the efficacy of surgical treatment and chemotherapy for SS remains poor. Therefore, the diagnosis and treatment of SS remain a significant challenge. This study aimed to analyze the mutated genes of primary SS (PSS) and recurrent SS (RSS), discover whether these sarcomas exhibit some potential mutated genes, and then predict associated microRNAs (miRNA) and circular RNAs (circRNA) by analyzing the mutated genes. We focused on the regulation mechanism of the circRNA-miRNA-mutated hub gene in PSS and RSS.Methods: We performed a comprehensive genomic analysis of four pairs of formalin-fixed paraffin-embedded samples of PSS and RSS, using Illumina human exon microarrays. The gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) function, and pathway enrichment of the mutated genes were analyzed, and the protein-protein interaction (PPI) network was forecast using String software 11.0. The hub genes were then obtained using the Molecular Complex Detection (MCODE) plug-in for Cytoscape 3.7.2 and were used to analyze overall survival (OS) using the Gene Expression Profiling Interactive Analysis (GEPIA) database. The corresponding miRNAs were obtained from the miRDB 5.0 and TargetScan 7.2 databases. The corresponding circRNAs of the hub genes were found through the miRNAs from these databases: Circbank, CircInteractome, and StarBase v2.0. Thereafter we set up a competing endogenous RNA (ceRNA) network with circRNA-miRNA and miRNA-messenger RNA (mRNA) pairs.Results: Using the chi-squared test, 391 mutated genes were screened using a significance level of p-values < 0.01 from the four pairs of PSS and RSS samples. A GO pathway analysis of 391 mutated genes demonstrated that differential expression mRNAs (DEmRNAs) might be bound up with the “positive regulation of neurogenesis,” “cell growth,” “axon part,” “cell−substrate junction,” or “protein phosphatase binding” of SS. The PPI network was constructed using 391 mutated genes, and 53 hub genes were identified (p < 0.05). Eight variant hub genes were discovered to be statistically significant using the OS analysis (p < 0.05). The circRNA-miRNA-mRNA (ceRNA) network was constructed, and it identified two circRNAs (hsa_circ_0070557 and hsa_circ_0070558), 10 miRNAs (hsa-let-7a-3p, hsa-let-7b-3p, hsa-let-7f-1-3p, hsa-let-7f-2-3p, hsa-mir-1244, hsa-mir-1197, hsa-mir-124-3p, hsa-mir-1249-5p, hsa-mir-1253, and hsa-mir-1271-5p) and five hub genes (CENPE, ENPP3, GPR18, MDC1, and PLOD2).Conclusion: This study screened novel biological markers and investigated the differentiated circRNA-miRNA-mutated hub gene axis, which may play a pivotal role in the nosogenesis of PSS and RSS. Some circRNAs may be deemed new diagnostic or therapeutic targets that could be conducive to the future clinical treatment of SS.

Screening and predicted value of potential biomarkers for breast cancer using bioinformatics analysis

“…Cytoscape (version 3.8.0) is an open-source bioinformatics tool used to generate visual molecular interaction networks and the plug-in Molecular Complex Detection (MCODE) can develop key gene modules in the network. For this, we set the following parameters in MCODE: Degree Cut-off = 2, Node Score Cut-off = 0.2, K-Core = 2 and Max Depth = 100 24 .…”

Exploring the effect of Yinzhihuang granules on alcoholic liver disease based on pharmacodynamics, network pharmacology and molecular docking

“…Cytoscape 3.7.2 software was then used to visualize the results and construct a PPI network. The PPI network was analyzed by the MCODE plug-in in Cytoscape 3.7.2 software, and the k-Core value was set to 5 to screen key protein modules [ 34 ].…”

Genetic variation within the pri-let-7f-2 in the X chromosome predicting stroke risk in a Chinese Han population from Liaoning, China: From a case-control study to a new predictive nomogram

“…Since the A allele could be a risk factor for IS, individuals with the AA genotype may have a higher risk of developing IS. Studies have linked the let-7f genes with tumor cell growth, migration, and differentiation (28,29). Therefore, previous studies focused on the role of the rs17276588 polymorphism in the development Clinical and demographic ischemic stroke (IS) risk factors in the female population according to the least absolute shrinkage and selection operator (LASSO) binary logistic regression model.…”

“…Since the A allele could be a risk factor for IS, individuals with the AA genotype may have a higher risk of developing IS. Studies have linked the let-7f genes with tumor cell growth, migration, and differentiation ( 28 , 29 ). Therefore, previous studies focused on the role of the rs17276588 polymorphism in the development of various cancers ( 30 ).…”