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

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.

Yao Q ，He YL ，Wang N ，Dong SS ，Tu He Ta Mi Shi ME ，Feng X ，Chen H ，Pang LJ ，Zou H ，Zhou WH ，Li F ，Qi Y ... -  《Frontiers in Molecular Biosciences》

Identification of lncRNA/circRNA-miRNA-mRNA ceRNA Network as Biomarkers for Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) accounts for the majority of liver cancer, with the incidence and mortality rates increasing every year. Despite the improvement of clinical management, substantial challenges remain due to its high recurrence rates and short survival period. This study aimed to identify potential diagnostic and prognostic biomarkers in HCC through bioinformatic analysis. Methods: Datasets from GEO and TCGA databases were used for the bioinformatic analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out by WebGestalt website and clusterProfiler package of R. The STRING database and Cytoscape software were used to establish the protein-protein interaction (PPI) network. The GEPIA website was used to perform expression analyses of the genes. The miRDB, miRWalk, and TargetScan were employed to predict miRNAs and the expression levels of the predicted miRNAs were explored via OncomiR database. LncRNAs were predicted in the StarBase and LncBase while circRNA prediction was performed by the circBank. ROC curve analysis and Kaplan-Meier (KM) survival analysis were performed to evaluate the diagnostic and prognostic value of the gene expression, respectively. Results: A total of 327 upregulated and 422 downregulated overlapping DEGs were identified between HCC tissues and noncancerous liver tissues. The PPI network was constructed with 89 nodes and 178 edges and eight hub genes were selected to predict upstream miRNAs and ceRNAs. A lncRNA/circRNA-miRNA-mRNA network was successfully constructed based on the ceRNA hypothesis, including five lncRNAs (DLGAP1-AS1, GAS5, LINC00665, TYMSOS, and ZFAS1), six circRNAs (hsa_circ_0003209, hsa_circ_0008128, hsa_circ_0020396, hsa_circ_0030051, hsa_circ_0034049, and hsa_circ_0082333), eight miRNAs (hsa-miR-150-5p, hsa-miR-19b-3p, hsa-miR-23b-3p, hsa-miR-26a-5p, hsa-miR-651-5p, hsa-miR-10a-5p, hsa-miR-214-5p and hsa-miR-486-5p), and five mRNAs (CDC6, GINS1, MCM4, MCM6, and MCM7). The ceRNA network can promote HCC progression via cell cycle, DNA replication, and other pathways. Clinical diagnostic and survival analyses demonstrated that the ZFAS1/hsa-miR-150-5p/GINS1 ceRNA regulatory axis had a high diagnostic and prognostic value. Conclusion: These results revealed that cell cycle and DNA replication pathway could be potential pathways to participate in HCC development. The ceRNA network is expected to provide potential biomarkers and therapeutic targets for HCC management, especially the ZFAS1/hsa-miR-150-5p/GINS1 regulatory axis.

Chen S ，Zhang Y ，Ding X ，Li W ... -  《Frontiers in Genetics》

Identification of a lncRNA/circRNA-miRNA-mRNA ceRNA Network in Alzheimer's Disease.

Su L ，Zhang Y ，Wang Y ，Wei H ... -  《Journal of Integrative Neuroscience》

Construction of endogenous RNA regulatory network for colorectal cancer based on bioinformatics.

Li Y ，Yuan F ，Lin Z ，Pan Y ... -  《-》

Construction of the circRNA-miRNA-mRNA Regulatory Network of an Abdominal Aortic Aneurysm to Explore Its Potential Pathogenesis.

Abdominal aortic aneurysm (AAA) is a progressive cardiovascular disease, which is a permanent and localized dilatation of the abdominal aorta with potentially fatal consequence of aortic rupture. Dysregulation of circRNAs is correlated with the development of various pathological events in cardiovascular diseases. However, the function of circRNAs in abdominal aortic aneurysm (AAA) is unknown and remains to be explored. This study is aimed at determining the regulatory mechanisms of circRNAs in AAAs. This study was aimed at exploring the underlying molecular mechanisms of abdominal aortic aneurysms based on the competing endogenous RNA (ceRNA) regulatory hypothesis of circRNA, miRNA, and mRNA. The expression profiles of circRNAs (GSE144431), miRNAs (GSE62179), and mRNAs (GSE7084, GSE57691, and GSE47472) in human tissue sample from the aneurysm group and normal group were obtained from the Gene Expression Omnibus database, respectively. The circRNA-miRNA-mRNA network was constructed by using Cytoscape 3.7.2 software; then, the protein-protein interaction (PPI) network was constructed by using the STRING database, and the hub genes were identified by using the cytoHubba plug-in. The circRNA-miRNA-hub gene regulatory subnetwork was formed to understand the regulatory axis of hub genes in AAAs. The present study identified 40 differentially expressed circRNAs (DECs) in the GSE144431, 90 differentially expressed miRNAs (DEmiRs) in the GSE62179, and 168 differentially expressed mRNAs (DEGs) with the same direction regulation (130 downregulated and 38 upregulated) in the GSE7084, GSE57691, and GSE47472 datasets identified regarding AAAs. The miRNA response elements (MREs) of three DECs were then predicted. Four overlapping miRNAs were obtained by intersecting the predicted miRNA and DEmiRs. Then, 17 overlapping mRNAs were obtained by intersecting the predicted target mRNAs of 4 miRNAs with 168 DEGs. Furthermore, the circRNA-miRNA-mRNA network was constructed through 3 circRNAs, 4 miRNAs, and 17 mRNAs, and three hub genes (SOD2, CCR7, and PGRMC1) were identified. Simultaneously, functional enrichment and pathway analysis were performed within genes in the circRNA-miRNA-mRNA network. Three of them (SOD2, CCR7, and PGRMC1) were suggested to be crucial based on functional enrichment, protein-protein interaction, and ceRNA network analysis. Furthermore, the expression of SOD2 and CCR7 may be regulated by hsa_circ_0011449/hsa_circ_0081968/hsa-let-7f-5p; the expression of PGRMC1 may be regulated by hsa_circ_0011449/hsa_circ_0081968-hsa-let-7f-5p/hsa-let-7e-5p. In conclusion, the ceRNA interaction axis we identified may be an important target for the treatment of abdominal aortic aneurysms. This study provided further understanding of the potential pathogenesis from the perspective of the circRNA-related competitive endogenous RNA network in AAAs.

Zhang H ，Bian C ，Tu S ，Yin F ，Guo P ，Zhang J ，Wu Y ，Yin Y ，Guo J ，Han Y ... -  《-》