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Updated: Aug 23, 2025
Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform
Published on: November 30, 2016
Reconstruction and Differential Expression Profiling Core Target Analyses of the circRNA-miRNA-mRNA Network Based on
Sai Xu1,2, Shouqiang Chen2, Menghe Zhang2
1Shandong University of Traditional Chinese Medicine, Jinan, China.
Abstract:
Ulcerative colitis (UC) is a common autoimmune disease worldwide. Circular RNA (circRNA) is a type of noncoding ribonucleic acids (ncRNAs). In addition to their roles in numerous biological processes, circRNAs are also linked to a vast range of diseases including UC. Although previous studies have examined many circRNAs, the physiological and pathological roles of the circRNA-associated competing endogenous RNA (ceRNA) network in UC remain unclear. Thus, we constructed a circRNA-miRNA-mRNA network based on the ceRNA hypothesis by analyzing data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) database. Genes with higher degree values than others in the ceRNA network were selected as central nodes when constructing the corresponding core subnetworks. To fully understand the biological function of the ceRNA network, we entered all differentially expressed mRNAs (DEmRNAs) from the ceRNA network into the Database for Annotation and Integrated Discovery (DAVID), which was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We further entered DEmRNAs into the STRING database for protein-protein interaction (PPI) network analysis. The results elucidated that the ceRNA network comprised 403 circRNA nodes, 5 miRNA nodes, 138 mRNA nodes, and 559 edges. Three core ceRNA subnetworks centered on hsa-miR-342-3p, hsa-miR-199a-5p, and hsa-miR-142-3p were reconstructed in this study. GO and KEGG enrichment analyses identified 167 enriched GO categories and 14 enriched KEGG pathway terms. The core PPI network was composed of 15 core targets, of which CD44, HIF1A, and MMP2 were the most significant. In summary, 3 hub miRNAs (hsa-miR-342-3p, hsa-miR-199a-5p, hsa-miR-142-3p) and 3 hub genes (CD44, HIF1A, and MMP2) might play an important role in the development of UC. These hub nodes, first proposed here, might also be used as potential diagnostic markers and therapeutic targets.
Insights
Circular RNAs (circRNAs) form a competing endogenous RNA (ceRNA) network crucial in ulcerative colitis (UC) pathogenesis. Key microRNAs and genes like CD44, HIF1A, and MMP2 may serve as potential diagnostic markers and therapeutic targets for UC.
Area of Science:
- Molecular Biology
- Genomics
- Immunology
Background:
- Ulcerative colitis (UC) is a prevalent autoimmune disease with unclear molecular mechanisms.
- Circular RNAs (circRNAs), a class of noncoding RNAs, are implicated in various diseases, including UC.
- The role of the circRNA-ceRNA network in UC pathophysiology requires further elucidation.
Purpose of the Study:
- To construct and analyze the circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network in UC.
- To identify key regulatory nodes within the UC ceRNA network.
- To explore the potential diagnostic and therapeutic implications of identified network components.
Main Methods:
- Utilized data from the NCBI Gene Expression Omnibus (GEO) database to build a circRNA-miRNA-mRNA network.
- Employed network analysis to identify central nodes and construct core subnetworks.
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses for differentially expressed mRNAs (DEmRNAs).
- Conducted protein-protein interaction (PPI) network analysis using the STRING database.
Main Results:
- The constructed ceRNA network included 403 circRNA, 5 miRNA, and 138 mRNA nodes.
- Three core subnetworks centered on hsa-miR-342-3p, hsa-miR-199a-5p, and hsa-miR-142-3p were identified.
- GO and KEGG analyses revealed significant biological pathways and categories.
- The core PPI network highlighted CD44, HIF1A, and MMP2 as significant hub genes.
Conclusions:
- The identified hub miRNAs (hsa-miR-342-3p, hsa-miR-199a-5p, hsa-miR-142-3p) and hub genes (CD44, HIF1A, MMP2) are potentially critical in UC development.
- These hub nodes represent promising candidates for novel diagnostic biomarkers and therapeutic targets for ulcerative colitis.
