ArticleInternational journal of molecular and cellular medicine2025
Integrated Bioinformatics and Experimental Validation of the hsa_circ_0000378/miR-205-5p/RAD51 ceRNA Axis in Breast Cancer.
Article in International journal of molecular and cellular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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 < 0.05). Differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEgenes) were derived from TCGA-BRCA RNA-Seq (1,091 tumors, 113 normals) and miRNA-Seq (1,078 tumors, 104 normals) data using DESeq2 (|log₂FC| > 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 hsa_circ_0000378/hsa-miR-205-5p/RAD51 axis was validated in 48 paired BC and adjacent non-tumor tissues by RT-qPCR. Results indicated hsa_circ_0000378 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 hsa_circ_0000378 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 hsa_circ_0000378 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 hsa_circ_0000378 (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 hsa_circ_0000378/hsa_miR-205-5p/RAD51 axis as a potential biomarker; mechanistic validation and larger cohorts are needed for clinical application.
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