Dataset Information

Circular RNA mediated gene regulation in human breast cancer: A bioinformatics analysis.

ABSTRACT: Circular RNAs (circRNAs) are a new acknowledged class of RNAs that has been shown to play a major role in several biological functions both in physiological and pathological conditions, operating as critical part of regulatory processes, like competing endogenous RNA (ceRNA) networks. The ceRNA hypothesis is a recently discovered molecular mechanism that adds a new key layer of post-transcriptional regulation, whereby various types of RNAs can reciprocally influence each other's expression competing for binding the same pool of microRNAs, even affecting disease development. In this study, we build a network of circRNA-miRNA-mRNA interactions in human breast cancer, called CERNOMA, that is a bipartite graph with one class of nodes corresponding to differentially expressed miRNAs (DEMs) and the other one corresponding to differentially expressed circRNAs (DEC) and mRNAs (DEGs). A link between a DEC (or DEG) and DEM is placed if it is predicted to be a target of the DEM and shows an opposite expression level trend with respect to the DEM. Within the CERNOMA, we highlighted an interesting deregulated circRNA-miRNA-mRNA triplet, including the up-regulated hsa_circRNA_102908 (BRCA1 associated RING domain 1), the down-regulated miR-410-3p, and the up-regulated ESM1, whose overexpression has been already shown to promote tumor dissemination and metastasis in breast cancer.

SUBMITTER: Fiscon G

PROVIDER: S-EPMC10370684 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Circular RNA mediated gene regulation in human breast cancer: A bioinformatics analysis.

Fiscon Giulia G Funari Alessio A Paci Paola P

PloS one 20230726 7

Circular RNAs (circRNAs) are a new acknowledged class of RNAs that has been shown to play a major role in several biological functions both in physiological and pathological conditions, operating as critical part of regulatory processes, like competing endogenous RNA (ceRNA) networks. The ceRNA hypothesis is a recently discovered molecular mechanism that adds a new key layer of post-transcriptional regulation, whereby various types of RNAs can reciprocally influence each other's expression compe ...[more]

PMID: 37494404

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Project description:BackgroundProstate cancer (PCa) is one of the most common malignant tumors worldwide. Accumulating evidence has suggested that circular RNAs (circRNAs) are involved in the development and progression of various cancers, and they show great potential as novel biomarkers. However, the underlying mechanisms and specific functions of most circRNAs in PCa remain unknown. Here, we aimed to identify circRNAs with potential roles in PCa from the PCa expression profile.MethodsWe used data downloaded from the Gene Expression Omnibus to identify circRNAs that were differentially expressed between PCa samples and adjacent non-tumor samples. Relative expression levels of identified circRNAs were validated by quantitative real-time PCR. Micro (mi)RNA response elements were predicted by the CircInteractome database, and miRNA target genes were predicted by miRDB, miRTarBase, and TargetScan databases. Gene ontology (GO) enrichment analysis and pathway analysis revealed the potential biological and functional roles of these target genes. A circRNA-miRNA-mRNA interaction network was constructed by Cytoscape. The interaction between circRNAs and miRNAs in PCa was thoroughly reviewed in the PubMed. Finally, the mRNA expression of these genes was validated by the Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The expression of proteins encoded by these genes was further validated by the Human protein Atlas (HPA) database.ResultsA total of 60 circRNAs that were differentially expressed between PCa and healthy samples were screened, of which 15 were annotated. Three circRNAs (hsa_circ_0024353, hsa_circ_0085494, hsa_circ_0031408) certified the criteria were studied. The results of quantitative real-time PCR demonstrated that the expression of hsa_circ_0024353 was significantly downregulated in PC-3 cells when compared with RWPE-1 cells, while the expression of hsa_circ_0031408 and hsa_circ_0085494 was significantly upregulated in PC-3 cells when compared with RWPE-1 cells. GO and Kyoto Encyclopedia of Genes and Genomes analyses found that target genes were mainly enriched in metabolic processes and pathways involving phosphoinositide 3-kinase-Akt signaling, hypoxia-inducible factor-1 signaling, p53 signaling, and the cell cycle. A total of 11 miRNA target genes showing differential expression between PCa and healthy samples were selected, and their mRNA and protein expression were validated by GEPIA and HPA databases, respectively. Of these, PDE7B, DMRT2, and TGFBR3 were identified as potentially playing a role in PCa progression. Finally, three circRNA-miRNA-mRNA interaction axes were predicted by bioinformatics: hsa_circ_0024353-hsa-miR-940-PDE7B, hsa_circ_0024353-hsa-miR-1253-DMRT2, and hsa_circ_0085494-hsa-miR-330-3p-TGFBR3.ConclusionThis study identified three circRNA-miRNA-mRNA interaction axes that might provide novel insights into the potential mechanisms underlying PCa development.

Project description:Circular RNA (circRNA) is closely related to tumorigenesis and cancer progression. Yet, the roles of cancer-specific circRNAs in the circRNA-related ceRNA network of breast cancer (BRCA) remain unclear. The aim of this study was to construct a ceRNA network associated with circRNA and to explore new therapeutic and prognostic targets and biomarkers for breast cancer. We downloaded the circRNA expression profile of BRCA from Gene Expression Omnibus (GEO) microarray datasets and downloaded the miRNA and mRNA expression profiles of BRCA from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were identified, and a competitive endogenous RNA (ceRNA) regulatory network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Gene ontology and pathway enrichment analyses were performed on mRNAs regulated by circRNAs in ceRNA networks. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network were performed. A total of 72 DEcircRNAs, 158 DEmiRNAs, and 2762 DE mRNAs were identified. The constructed ceRNA network contains 60 circRNA-miRNA pairs and 140 miRNA-mRNA pairs, including 40 circRNAs, 30 miRNAs, and 100 mRNAs. Functional enrichment indicated that DEmRNAs regulated by DEcircRNAs in ceRNA networks were significantly enriched in the PI3K-Akt signaling pathway, microRNAs in cancer, and proteoglycans in cancer. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network showed that 13 mRNAs and 6 miRNAs were significantly associated with overall survival, and 48 miRNA-mRNA interaction pairs had a significant negative correlation. A PPI network was established, and 21 hub genes were determined from the network. This study provides an effective bioinformatics basis for further understanding of the molecular mechanisms and predictions of breast cancer. A better understanding of the circRNA-related ceRNA network in BRCA will help identify potential biomarkers for diagnosis and prognosis.

Dataset Information

Circular RNA mediated gene regulation in human breast cancer: A bioinformatics analysis.

Publications

Circular RNA mediated gene regulation in human breast cancer: A bioinformatics analysis.

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