Identification of circRNA-miRNA-mRNA Regulatory Network in Bladder Cancer by Integrated Analysis.

Bladder cancer (BC) is a common malignant tumor in the urinary system with high mortality and recurrence rates. This study sought to identify crucial circular RNAs (circRNAs) associated with BC. The mRNA, miRNA, and circRNA expression profiles of BC were downloaded from GEO database. The differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) were identified using bioinformatics method. Combining circRNA-miRNA pairs with miRNA-mRNA pairs, the competing endogenous RNA (ceRNA; DEcircRNA-DEmi-RNA-DEmRNA) regulatory network was constructed. Functional annotation of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network were performed. qRT-PCR validation was performed. A total of 4,003 DEmRNAs, 25 DEmiRNAs, and 119 DEcircRNAs were obtained. The ceRNA network contained 18 circRNA-miRNA pairs and 699 mi-RNA-mRNA pairs, including 17 circRNAs, 4 miRNAs, and 624 mRNAs. Functional annotation of DEmRNAs in ceRNA regulatory network revealed that these DEmRNAs were significantly enriched in glycerolipid metabolism, p53 signaling pathway, and oocyte meiosis. Except for hsa_circ_0028173, expression of the others in the qRT-PCR results was consistent with that in our integrated analysis, generally. We speculate that hsa_circ_0008035/hsa-miR-107/MSRB3 and hsa_circ_0028173/hsa-miR-338-3p/TPX2/GATA3 interaction pairs may play a vital role in BC.

Chen P ，Chen J ，He L ，Du C ，Wang X ... -  《-》

Identification of circular RNA-microRNA-messenger RNA regulatory network in hepatocellular carcinoma by integrated analysis.

Hepatocellular carcinoma (HCC) is the most common types of hepatic malignancies. This study aimed to better understand the pathogenesis of HCC and may help facilitate the improvement of the diagnostic of HCC. The mRNA and miRNA expression profiles of HCC, which was retrieved from The Cancer Genome Atlas database, and the circRNA expression profiles of HCC, which was retrieved from Gene Expression Omnibus database, were included in this study to perform an integrated analysis. The differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were identified, and competing endogenous RNA (ceRNA) (DEcircRNA-DEmiRNA-DEmRNA) regulatory network was conducted. Functional annotation of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network was performed. Quantitative real-time polymerase chain reaction validation of the expression of the selected DEmRNAs, DEmiRNAs, and DEcircRNAs was performed. A total of 2982 DEmRNAs, 144 DEmiRNAs, and 264 DEcircRNAs were obtained. The ceRNA network contained 61 circRNA-miRNA pairs and 1149 miRNA-mRNA pairs, including 48 circRNAs, 30 miRNAs, and 1149 mRNAs. Functional annotation of DEmRNAs in ceRNA regulatory network revealed that these DEmRNAs were significantly enriched in tryptophan metabolism, fatty acid metabolism, and pathways in cancer. Except for ARNT2 and hsa-miR-214-3p, expression of the others in the quantitative real-time polymerase chain reaction results was consistent with that in our integrated analysis, generally. We speculate that hsa_circRNA_104268/hsa-miR-214-3p/E2F2, hsa_circRNA_104168/hsa-miR-139-5p/HRAS, and hsa_circRNA_104769/hsa-miR-93-5p/JUN interaction pairs may play a vital role in HCC. This study expected to provide a novel insight into the pathogenesis and therapy of HCC from the circRNA-miRNA-mRNA network view.

Sun X ，Ge X ，Xu Z ，Chen D ... -  《-》

Identification of Circular RNA-MicroRNA-Messenger RNA Regulatory Network in Atrial Fibrillation by Integrated Analysis.

Circular RNA (circRNA) is a noncoding RNA that forms a closed-loop structure, and its abnormal expression may cause disease. We aimed to find potential network for circRNA-related competitive endogenous RNA (ceRNA) in atrial fibrillation (AF). The circRNA, miRNA, and mRNA expression profiles in the heart tissue from AF patients were retrieved from the Gene Expression Omnibus database and analyzed comprehensively. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified, followed by the establishment of DEcircRNA-DEmiRNA-DEmRNA regulatory network. Functional annotation analysis of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network was performed. In vitro experiment and electronic validation were used to validate the expression of DEcircRNAs, DEmiRNAs, and DEmRNAs. A total of 1611 DEcircRNAs, 51 DEmiRNAs, and 1250 DEmRNAs were identified in AF. The DEcircRNA-DEmiRNA-DEmRNA network contained 62 circRNAs, 14 miRNAs, and 728 mRNAs. Among which, two ceRNA regulatory pairs of hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 were identified. In addition, six miRNA-mRNA regulatory pairs including hsa-miR-34c-5p-INMT, hsa-miR-1253-DDIT4L, hsa-miR-508-5p-SMOC2, hsa-miR-943-ACTA1, hsa-miR-338-3p-WIPI1, and hsa-miR-199a-3p-RAP1GAP2 were also obtained. MTOR was a significantly enriched signaling pathway of host gene of DEcircRNAs. In addition, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy were remarkably enriched signaling pathways of DEmRNAs in DEcircRNA-DEmiRNA-DEmRNA regulatory network. The expression validation of hsa-circRNA-402565, hsa-miR-34c-5p, hsa-miR-188-5p, SPON1, DDIT4L, SMOC2, and WIPI1 was consistent with the integrated analysis. We speculated that hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 interaction pairs may be involved in AF.

Liu T ，Zhang G ，Wang Y ，Rao M ，Zhang Y ，Guo A ，Wang M ... -  《-》

Comprehensive Analysis of circRNA-miRNA-mRNA Network in Cervical Squamous Cell Carcinoma by Integrated Analysis.

Cervical squamous cell carcinoma (CSCC) seriously affects women's health worldwide, and it is of great significance to illuminate the specific role of circRNAs in CSCC. Three mRNA datasets, two miRNA datasets and one circRNA dataset of CSCC, downloaded from GEO, were utilized in this study. Differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and circRNAs (DEcircRNAs) were identified, and a ceRNA (DEcircRNA-DEmiRNA-DEmRNA) regulatory network was constructed. GO and pathway analyses of DEcircRNAs and DEmRNAs in the ceRNA regulatory network were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) validation of the expression of the selected DEmRNAs, DEmiRNAs and DEcircRNAs was performed. A total of 1356 DEmRNAs, 13 DEmiRNAs and 77 DEcircRNAs were obtained. The ceRNA network contained 3 circRNA-miRNA pairs and 158 miRNA-mRNA pairs, including 3 circRNAs, 3 miRNAs, and 138 mRNAs. Functional annotation of DEmRNAs in the ceRNA regulatory network revealed that these DEmRNAs were significantly enriched in cell cycle, p53 signalling pathway and DNA replication. The qRT-PCR results were generally consistent with those of our integrated analysis. In conclusion, we speculate that the regulation of the hsa_circ_0000069/hsa-miR-125b-5p/CDKN2A and hsa_circ_0020594/hsa-let-7c-5p/CCNB2 axes may be involved in CSCC.

Wu Q ，Liu P ，Lao G ，Liu Y ，Zhang W ，Ma C ... -  《OncoTargets and Therapy》

Construction and Bioinformatics Analysis of circRNA-miRNA-mRNA Network in Acute Myocardial Infarction.

Background: Acute myocardial infarction (AMI) is one of the main fatal diseases of cardiovascular diseases. Circular RNA (circRNA) is a non-coding RNA (ncRNA), which plays a role in cardiovascular disease as a competitive endogenous RNA (ceRNA). However, their role in AMI has not been fully clarified. This study aims to explore the mechanism of circRNA-related ceRNA network in AMI, and to identify the corresponding immune infiltration characteristics. Materials and Methods: The circRNA (GSE160717), miRNA (GSE24548), and mRNA (GSE60993) microarray datasets of AMI were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified by the "limma" package. After integrating the circRNA, miRNA and mRNA interaction, we constructed a circRNA-miRNA-mRNA network. The "clusterProfiler" package and String database were used for functional enrichment analysis and protein-protein interaction (PPI) analysis, respectively. After that, we constructed a circRNA-miRNA-hub gene network and validated the circRNAs and mRNAs using an independent dataset (GSE61144) as well as qRT-PCR. Finally, we used CIBERSORTx database to analyze the immune infiltration characteristics of AMI and the correlation between hub genes and immune cells. Results: Using the "limma" package of the R, 83 DEcircRNAs, 54 DEmiRNAs, and 754 DEmRNAs were identified in the microarray datasets of AMI. Among 83 DEcircRNAs, there are 55 exonic DEcircRNAs. Then, a circRNA-miRNA-mRNA network consists of 21 DEcircRNAs, 11 DEmiRNAs, and 106 DEmRNAs were predicted by the database. After that, 10 hub genes from the PPI network were identified. Then, a new circRNA-miRNA-hub gene network consists of 14 DEcircRNAs, 7 DEmiRNAs, and 9 DEmRNAs was constructed. After that, three key circRNAs (hsa_circ_0009018, hsa_circ_0030569 and hsa_circ_0031017) and three hub genes (BCL6, PTGS2 and PTEN) were identified from the network by qRT-PCR. Finally, immune infiltration analysis showed that hub genes were significantly positively correlated with up-regulated immune cells (neutrophils, macrophages and plasma cells) in AMI. Conclusion: Our study constructed a circRNA-related ceRNA networks in AMI, consists of hsa_circ_0031017/hsa-miR-142-5p/PTEN axis, hsa_circ_0030569/hsa-miR-545/PTGS2 axis and hsa_circ_0009018/hsa-miR-139-3p/BCL6 axis. These three hub genes were significantly positively correlated with up-regulated immune cells (neutrophils, macrophages and plasma cells) in AMI. It helps improve understanding of AMI mechanism and provides future potential therapeutic targets.

Zhou J ，He S ，Wang B ，Yang W ，Zheng Y ，Jiang S ，Li D ，Lin J ... -  《Frontiers in Genetics》