Elucidation of molecular links between obesity and cancer through microRNA regulation

BMC Medical Genomics

Zheng Xu¹  Haluk Dogan²  Jiang Shu²  Juan Cui²  Zeynep Hakguder² 

[1] Department of Mathematics and Statistics, Wright State University, 45435, Dayton, OH, USA;Systems Biology and Biomedical Informatics Lab, Department of Computer Science and Engineering University of Nebraska-Lincoln, 68588-0115, Lincoln, NE, USA;

关键词: MicroRNA;    Obesity;    Cancer;    MicroRNA regulation;   

DOI  :  10.1186/s12920-020-00797-8

来源: Springer

【 摘 要 】

BackgroundObesity contributes to high cancer risk in humans and the mechanistic links between these two pathologies are not yet understood. Recent emerging evidence has associated obesity and cancer with metabolic abnormalities and inflammation where microRNA regulation has a strong implication.MethodsIn this study, we have developed an integrated framework to unravel obesity-cancer linkage from a microRNA regulation perspective. Different from traditional means of identifying static microRNA targets based on sequence and structure properties, our approach focused on the discovery of context-dependent microRNA-mRNA interactions that are potentially associated with disease progression via large-scale genomic analysis. Specifically, a meta-regression analysis and the integration of multi-omics information from obesity and cancers were presented to investigate the microRNA regulation in a dynamic and systematic manner.ResultsOur analysis has identified a total number of 2,143 unique microRNA-gene interactions in obesity and seven types of cancer. Common interactions in obesity and obesity-associated cancers are found to regulate genes in key metabolic processes such as fatty acid and arachidonic acid metabolism and various signaling pathways related to cell growth and inflammation. Additionally, modulated co-regulations among microRNAs targeting the same functional processes were reflected through the analysis.ConclusionWe demonstrated the statistical modeling of microRNA-mediated gene regulation can facilitate the association study between obesity and cancer. The entire framework provides a powerful tool to understand multifaceted gene regulation in complex human diseases that can be generalized in other biomedical applications.

【 授权许可】

CC BY