Petrović Nina, Essack Magbubah, Šami Ahmad, Perry George, Gojobori Takashi, Isenović Esma R, Bajić Vladan P
Laboratory for Radiobiology and Molecular Genetics, Department of Health and Environment, "VINČA "Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12-14, 11001 Belgrade, Serbia; Department for Experimental Oncology, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), Computational Bioscience Research Center, Computer (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
Comput Biol Chem. 2023 Oct;106:107925. doi: 10.1016/j.compbiolchem.2023.107925. Epub 2023 Jul 16.
MicroRNAs (miRNAs) are involved in the regulation of various cellular processes including pathological conditions. MiRNA networks have been extensively researched in age-related degenerative diseases, such as cancer, Alzheimer's disease (AD), and heart failure. Thus, miRNA has been studied from different approaches, in vivo, in vitro, and in silico including miRNA networks. Networks linking diverse biomedical entities unveil information not readily observable by other means. This work focuses on biological networks related to Breast cancer susceptibility 1 (BRCA1) in AD and breast cancer (BC). Using various bioinformatics approaches, we identified subnetworks common to AD and BC that suggest they are linked. According to our results, miR-107 was identified as a potentially good candidate for both AD and BC treatment (targeting BRCA1/2 and PTEN in both diseases), accompanied by miR-146a and miR-17. The analysis also confirmed the involvement of the miR-17-92 cluster, and miR-124-3p, and highlighted the importance of poorly researched miRNAs such as mir-6785 mir-6127, mir-6870, or miR-8485. After filtering the in silico analysis results, we found 49 miRNA molecules that modulate the expression of at least five genes common to both BC and AD. Those 49 miRNAs regulate the expression of 122 genes in AD and 93 genes in BC, from which 26 genes are common genes for AD and BC involved in neuron differentiation and genesis, cell differentiation and migration, regulation of cell cycle, and cancer development. Additionally, the highly enriched pathway was associated with diabetic complications, pointing out possible interplay among molecules underlying BC, AD, and diabetes pathology.
微小RNA(miRNA)参与包括病理状况在内的各种细胞过程的调控。miRNA网络已在与年龄相关的退行性疾病,如癌症、阿尔茨海默病(AD)和心力衰竭中得到广泛研究。因此,人们从体内、体外和计算机模拟等不同方法,包括miRNA网络,对miRNA进行了研究。连接不同生物医学实体的网络揭示了其他方法不易观察到的信息。这项工作聚焦于AD和乳腺癌(BC)中与乳腺癌易感基因1(BRCA1)相关的生物网络。通过各种生物信息学方法,我们确定了AD和BC共有的子网络,表明它们之间存在联系。根据我们的结果,miR - 107被确定为AD和BC治疗的潜在良好候选者(在两种疾病中靶向BRCA1/2和PTEN),同时还有miR - 146a和miR - 17。分析还证实了miR - 17 - 92簇和miR - 124 - 3p的参与,并突出了研究较少的miRNA如mir - 6785、mir - 6127、mir - 6870或miR - 8485的重要性。在筛选计算机模拟分析结果后,我们发现49个miRNA分子调节BC和AD共有的至少五个基因的表达。这49个miRNA调节AD中的122个基因和BC中的93个基因,其中26个基因是AD和BC的共同基因,参与神经元分化和发生、细胞分化和迁移、细胞周期调控以及癌症发展。此外,高度富集的通路与糖尿病并发症相关,指出了BC、AD和糖尿病病理背后分子之间可能的相互作用。