en Cancer Cancer Original Article Original Article <div style="text-align: justify;"><span style="font-family:Tahoma;"><span style="font-size:12px;"><span style="line-height:107%">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&#39;s diagnostic potential (AUC=0.83, 95% CI: 0.74&ndash;0.90, sensitivity=0.81, specificity=0.55), followed by hsa_circ_0000378 (AUC=0.75, 95% CI: 0.65&ndash;0.85, sensitivity=0.71, specificity=0.77), and hsa-miR-205-5p (AUC=0.66, 95% CI: 0.56&ndash;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.</span></span></span></div> Breast Cancer, ceRNA network, Bioinformatic, Circular RNA, Micro RNA, Real-Time PCR, RAD51 994 1013 http://ijmcmed.org/browse.php?a_code=A-10-68-1&slc_lang=en&sid=1 Ali Abbasi aliabbasibiochemistry@gmail.com 100319475328460036783 100319475328460036783 No Student Research Committee, Babol University of Medical Sciences, Babol, Iran. Nahid Nafisi Nafissi.n@iums.ac.ir 100319475328460036784 100319475328460036784 No Surgery Department, Rasoul Akram Hospital Clinical Research Development Center (RCRDC), Iran University of Medical Sciences, Tehran, Iran Pejman Morovat pejmanmorovat@yahoo.com 100319475328460036785 100319475328460036785 No Department of Medical Biotechnology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran Mitra NourBakhsh Mitra.nourbakhsh@gmail.com 100319475328460036786 100319475328460036786 No Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran Mahdi Sepidarkish mahdi.sepidarkish@gmail.com 100319475328460036787 100319475328460036787 No Department of Biostatistics and Epidemiology, School of Public Health, Babol University of Medical Sciences, Babol, Iran mohamadreza Ahmadifard mr.ahmadifard@gmail.com 100319475328460036788 100319475328460036788 No Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran Arash Majd Ashrafi arash.biologist@gmail.com 100319475328460036789 100319475328460036789 No ellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical SCciences, Babol, Iran Mahdi Pour Amir pouramir@yahoo.com 100319475328460036790 100319475328460036790 Yes Department of Medical Biochemistry, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran