Breast cancer (BC) remains the leading cause of cancer-related mortality in women worldwide, primarily due to its high invasiveness and therapeutic resistance. This study explores the role of noncoding RNAs, circular RNAs (circRNAs), in BC progression through a competing endogenous RNA (ceRNA) network. Three GEO circRNA microarray datasets (GSE101123, GSE165884, GSE182471) were retrieved, normalized, and batch-corrected using ComBat. Differentially expressed circRNAs (DEcircRNAs) were identified via limma (|log₂FC| > 1, FDR 1, FDR < 0. 05). CircRNAs harboring miRNA response elements (MREs) were selected via CSCD, and miRNA-mRNA interactions predicted through TarBase, prioritizing upregulated DEgenes. A ceRNA network was constructed in Cytoscape based on expression concordance. The hsacirc₀000378/hsa-miR-205-5p/RAD51 axis was validated in 48 paired BC and adjacent non-tumor tissues by RT-qPCR. Results indicated hsacirc₀000378 upregulation (2. 74-fold, p<0. 001), hsa-miR-205-5p downregulation (0. 64-fold, p=0. 0022), and RAD51 upregulation (3. 46-fold, p<0. 001) in tumors. Spearman correlations showed negative associations between hsacirc₀000378 and hsa-miR-205-5p (r = -0. 474, p<0. 001), hsa-miR-205-5p and RAD51 (r = -0. 383, p<0. 001), and positive between hsacirc₀000378 and RAD51 (r = 0. 497, p<0. 001), supporting ceRNA regulation. ROC analysis revealed RAD51's diagnostic potential (AUC=0. 83, 95% CI: 0. 74-0. 90, sensitivity=0. 81, specificity=0. 55), followed by hsacirc₀000378 (AUC=0. 75, 95% CI: 0. 65-0. 85, sensitivity=0. 71, specificity=0. 77), and hsa-miR-205-5p (AUC=0. 66, 95% CI: 0. 56-0. 76, sensitivity=0. 69, specificity=0. 55). These results propose the hsacirc₀000378/hsaₘiR-205-5p/RAD51 axis as a potential biomarker; mechanistic validation and larger cohorts are needed for clinical application.
Abbasi et al. (Wed,) studied this question.