Integrative Expression,Survival Analysis and Cellular miR-2909 Molecular Interplay in MRN Complex Check Point Sensor Genes (MRN-CSG) Involved in Breast Cancer |
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| Affiliation: | 1. Department of Breast Oncology, H. Lee Moffitt Cancer Center, Moffitt Cancer Center, Tampa, FL;2. Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, FL;1. Department of Plastic Surgery, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;2. Department of Plastic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden;3. Dept Plastic Surgery, Landsspital, Raykavik, Iceland;1. Plastic and Reconstructive Surgery Unit, Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu, Sabah, Malaysia;2. Reconstructive Sciences Unit, Department of Surgery, Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia;3. Reconstructive Sciences Unit, Faculty of Medicine and Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia;4. Department of Surgery, Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia;5. Department of Radiology, Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia;1. Department of breast surgery, Herlev-Gentofte Hospital, Gentofte, Denmark;2. Department of plastic- and breast surgery, Sealand University hospital Roskilde, Roskilde, Denmark;3. Department of pathology, Rigshospitalet, København Ø, Denmark;4. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, København Ø, Denmark;1. Breast Unit, Department of Gynecology. Hospital Universitari Mútua Terrassa. Universitat de Barcelona. Terrassa. Spain;2. Breast Unit, Department of Pathology. Hospital Universitari Mútua Terrassa. Universitat de Barcelona. Terrassa. Spain;3. Breast Unit, Department of Nuclear Medicine. Hospital Universitari Mútua Terrassa. Universitat de Barcelona. Terrassa. Spain |
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| Abstract: | BackgroundBreast cancer, an emerging global challenge, is evidenced by recent studies of miRNAs involvement in DNA repair gene variants (MRE11, RAD50, and NBN as checkpoint sensor genes (CSG) – MRN-CSG). The identification of various mutations in MRN-CSG and their interactions with miRNAs is still not understood. The emerging studies of miR-2909 involvement in other cancers led us to explore its role as molecular mechanistic marker in breast cancer.Materials and MethodsThe genomic and proteomic data of MRN-CSG of breast cancer patients (8426 samples) was evaluated to identify the mutation types linked with the patient's survival rate. Additionally, molecular, 3D-structural and functional analysis was performed to identify miR-2909 as regulator of MRN-CSG.ResultsThe genomic and proteomic data analysis shows genetic alterations with majority of missense mutations [RAD50 (0.7%), MRE11 (1.5%), and NBN (11%)], though with highest MRE11 mRNA expression in invasive ductal breast carcinoma as compared to other breast cancer types. The Kaplan–Meier survival curves suggest higher survival rate for unaltered groups as compared to the altered group. Network analysis and disease association of miR-2909 and MRN-CSG shows strong interactions with other partners. The molecular hybridization between miR-2909-RAD50 and miR-2909-MRE11 complexes showed thermodynamically stable structures. Further, argonaute protein, involved in RNA silencing, docking studies with miR-MRE11-mRNA and miR-RAD50-mRNA hybridized complexes showed strong binding affinity.ConclusionThe results suggest that miR-2909 forms strong thermodynamically stable molecular hybridized complexes with MRE11 and RAD50 mRNAs which further strongly interacts with argonaute protein to show potential molecular mechanistic role in breast cancer. |
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