Sercan Ergun1,2, Sezgin Gunes3,4, Neslihan Hekim1, Sandro C Esteves5,6,7. 1. Department of Medical Biology, Faculty of Medicine, Ondokuz Mayis University, 55139, Samsun, Turkey. 2. Department of Multidisciplinary Molecular Medicine, Graduate Institute, Ondokuz Mayis University, Samsun, Turkey. 3. Department of Medical Biology, Faculty of Medicine, Ondokuz Mayis University, 55139, Samsun, Turkey. sgunes@omu.edu.tr. 4. Department of Multidisciplinary Molecular Medicine, Graduate Institute, Ondokuz Mayis University, Samsun, Turkey. sgunes@omu.edu.tr. 5. ANDROFERT, Andrology and Human Reproduction Clinic, Campinas, SP, Brazil. 6. Department of Surgery (Division of Urology), University of Campinas (UNICAMP), Campinas, SP, Brazil. 7. Faculty of Health, Aarhus University, Aarhus, Denmark.
Abstract
PURPOSE: Microdeletion on Y-chromosome is a well-known genetic cause of infertility in azoospermic and oligozoospermic men. RNA transcripts possess microRNA (miRNA) response elements (MRE) that may interact with competing endogenous RNAs (ceRNA), thus repressing their activity. MiRNAs originally targeting transcripts of genes deleted in the Y-chromosome azoospermia factor (AZF) region are expected to be oriented to binding sites of new targets. We investigated miRNAs targeting genes of each AZF locus (AZFa, AZFb, AZFb-c, and AZFc) to determine their corresponding ceRNA using in silico analysis. METHODS: The miRNAs targeting most of the genes deleted in each AZF locus were identified using the miRWalk database. Twelve miRNAs exhibiting potential ceRNA activity were identified and analyzed using the ComiR database. Detected ceRNAs for each AZF locus were processed in the GeneMANIA database for interaction prediction, and the most probably interacted genes were identified. RESULTS: RPPA2, TMED3, STX7 and ATRX, GOGLB1, KMT2C genes were found potential ceRNAs for the AZFa and AZFb regions, respectively. Furthermore, CNB5, KCNC4, NDUFS1 and TROBP, HEMK1, and ORAI2 genes were the potential ceRNAs for the partially AZFb-c-overlapped region and AZFc regions, respectively. CONCLUSION: Our findings suggest that AZF loci deletion may change post-transcriptional regulation of gene expression through miRNA competition.
PURPOSE: Microdeletion on Y-chromosome is a well-known genetic cause of infertility in azoospermic and oligozoospermic men. RNA transcripts possess microRNA (miRNA) response elements (MRE) that may interact with competing endogenous RNAs (ceRNA), thus repressing their activity. MiRNAs originally targeting transcripts of genes deleted in the Y-chromosome azoospermia factor (AZF) region are expected to be oriented to binding sites of new targets. We investigated miRNAs targeting genes of each AZF locus (AZFa, AZFb, AZFb-c, and AZFc) to determine their corresponding ceRNA using in silico analysis. METHODS: The miRNAs targeting most of the genes deleted in each AZF locus were identified using the miRWalk database. Twelve miRNAs exhibiting potential ceRNA activity were identified and analyzed using the ComiR database. Detected ceRNAs for each AZF locus were processed in the GeneMANIA database for interaction prediction, and the most probably interacted genes were identified. RESULTS: RPPA2, TMED3, STX7 and ATRX, GOGLB1, KMT2C genes were found potential ceRNAs for the AZFa and AZFb regions, respectively. Furthermore, CNB5, KCNC4, NDUFS1 and TROBP, HEMK1, and ORAI2 genes were the potential ceRNAs for the partially AZFb-c-overlapped region and AZFc regions, respectively. CONCLUSION: Our findings suggest that AZF loci deletion may change post-transcriptional regulation of gene expression through miRNA competition.