International Journal of Molecular and Cellular Medicine (IJMCM)
Babol University of Medical Sciences
Tue, Dec 23, 2025
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Volume 0 - Int J Mol Cell Med (Inprees)
Int J Mol Cell Med 2025, 0 - Int J Mol Cell Med (Inprees): 0-0 |
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Abbasi A, Nafisi N, Morovat P, NourBakhsh M, Sepidarkish M, Ahmadifard M, et al . Integrated Bioinformatics and Experimental Validation of the hsa_circ_0000378/miR-205-5p/RAD51 ceRNA Axis in Breast Cancer. Int J Mol Cell Med 2025;
URL: http://ijmcmed.org/article-1-2623-en.html
URL: http://ijmcmed.org/article-1-2623-en.html
Ali Abbasi1 
, Nahid Nafisi2 , Pejman Morovat3 , Mitra NourBakhsh4 , Mahdi Sepidarkish5 , Mohamadreza Ahmadifard6 , Arash Majd Ashrafi7 , Mahdi Pour Amir8
, Nahid Nafisi2 , Pejman Morovat3 , Mitra NourBakhsh4 , Mahdi Sepidarkish5 , Mohamadreza Ahmadifard6 , Arash Majd Ashrafi7 , Mahdi Pour Amir8
1- Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
2- Surgery Department, Rasoul Akram Hospital Clinical Research Development Center (RCRDC), Iran University of Medical Sciences, Tehran, Iran
3- Department of Medical Biotechnology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
4- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
5- Department of Biostatistics and Epidemiology, School of Public Health, Babol University of Medical Sciences, Babol, Iran
6- Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
7- ellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical SCciences, Babol, Iran
8- Department of Medical Biochemistry, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran ,pouramir@yahoo.com
2- Surgery Department, Rasoul Akram Hospital Clinical Research Development Center (RCRDC), Iran University of Medical Sciences, Tehran, Iran
3- Department of Medical Biotechnology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
4- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
5- Department of Biostatistics and Epidemiology, School of Public Health, Babol University of Medical Sciences, Babol, Iran
6- Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
7- ellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical SCciences, Babol, Iran
8- Department of Medical Biochemistry, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran ,
Abstract: (5 Views)
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.
Keywords: Breast Cancer, ceRNA network, Bioinformatic, Circular RNA, Micro RNA, Real-Time PCR, RAD51
Type of Study: Original Article |
Subject:
Cancer
Received: 2025/06/28 | Accepted: 2025/09/22 | Published: 2025/07/28
Received: 2025/06/28 | Accepted: 2025/09/22 | Published: 2025/07/28
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