The Development of the Regulatory Net of microRNA–mRNA Interactions in General Biological Processes and Signaling Pathways in Breast Cancer

The biological heterogeneity of breast cancer complicates the choice of an effective treatment. The participation of microRNAs in the regulation of target mRNAs in biological processes and signaling cascades makes them suitable for use as diagnostic and prognostic markers or targets for therapy.

The aim of our work was to analyze the expression of microRNAs in paired samples of tumor and adjacent normal breast tissue and to assess their potential cooperative participation in biological processes and signaling pathways.

The microRNA expression was analyzed using Taq Man MicroRNA Assay Kits. The differences between the groups were assessed using the nonparametric Mann–Whitney U test. Spearman's correlation coefficient was calculated to identify co-expression. Functional annotation and enrichment analysis concerning Gene Ontology terms and KEGG signaling pathways were performed in R (clusterProfiler, org.Hs.eg.db, enrichplot) (adj. p-value<0.05 according to Benjamini–Hochberg procedure).

Positive expression correlations were found for seven pairs of microRNAs: miR-127-5p/miR-125b-5p (Rs=0.47), miR-148a-3p/miR-125b-5p (Rs=0.44), miR-148a-3p/miR-132-3p (Rs=0.46), miR-193a-5p/miR-127-5p (Rs=0.51), miR-24-2-5p/miR-127-5p (Rs=0.43), miR-34b-3p/miR-193a-5p (Rs=0.54), and miR-34b-3p/miR-24-2-5p (Rs=0.58). Enrichment analysis revealed overlapping processes for four microRNA pairs: miR-127-5p/miR-125b-5p (28), miR-148a-3p/miR-125b-5p (355), miR-148a-3p/miR-132-3p (195), and miR-34b-3p/miR-193a-5p (three common processes). We constructed a regulatory net of microRNA–mRNA interactions. MiR-125b-5p was the central node in the net; it bound to multiple oncogenic and suppressor genes, including APC, BCL2, STAT3, and LDLR. Coincident targets such as APC and CDKN1A bound by multiple microRNAs suggest coordinated post-transcriptional regulation.

The constructed net demonstrates potentially significant regulatory axes linking microRNAs and their targets, highlighting their possible common roles in breast cancer pathogenesis.