Co‑expression network analysis identified specific miRNAs and genes in association with slow‑transit constipation.

Abstract

The pathogenesis of slow-transit constipation (STC) remains largely unclear, with the roles of microRNAs (miRs/miRNAs) yet to be determined. Co-expression network analysis of miRNAs in STC is crucial to elucidating potential underlying mechanisms. Weighted gene correlation network analysis was performed in the miRNA expression profile of STC (GSE57969). The key miRNA target genes were further functionally enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). A Protein-Protein Interaction (PPI) network was constructed, with a total of 12 color-clustered modules determined. Seven key miRNAs were established, including five miRNAs from the turquoise module (hsa-miR-20b, hsa-miR-128, hsa-miR-129-3p, hsa-miR-30b and hsa-miR-340), one miRNA from the blue module (hsa-miR-619) and one from the black module (hsa-miR-486-3p). A total of 2,077 key miRNA target genes were predicted. GO analysis revealed that the ‘protein modification process’ and ‘cellular protein modification process’ were the most significantly enriched processes in the ‘Biological Processes’ category, whereas the ‘nucleoplasm’ in ‘Cellular Components’ and ‘enzyme binding’ in ‘Molecular Functions’ were the most significantly enriched processes. The ‘cAMP signalling pathway’ was the top KEGG pathway. The hub genes identified from the PPI network included calmodulin (CALM)2, CALM1, histone deacetylase (HDAC)3, glycogen synthase kinase 3 β, HDAC9, heat-shock protein family A member 8, G-protein subunit γ (GNG)13, HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1, GNG10 and GNG7. This bioinformatics analysis demonstrated co-expressed miRNA networks with insightful genes and pathways associated with STC.