Volume 29, Issue 3
DOI: 10.24205/03276716.2020.927
Comprehensive Analysis of Multi-Regulator-Driven Dysfunctional Modules in Calculous Cholecystitis
Abstract
Cholecystitis is inflammation of the gallbladder caused by obstruction of the cystic duct and bacterial invasion, and is often associated with gallstones, which is also called calculous cholecystitis. Its pathogenesis is regulated by genes and the environment. However, this has not been clearly stated in previous studies. Therefore, based on dysfunctional modules in cholecystolithiasis with cholecystitis, this study attempted to describe the multidimensional adjustment landscape of the disease from a global perspective. Functional modules were identified from tissue-specific expression proteinsassociated interaction network in calculous cholecystitis. These tissue-specific expression proteins and their interactors often played an important role in calculous cholecystitis. Functional enrichment results indicated that they were mainly involved in various immune responses, inflammatory responses, cholecystokinin and cholesterol-related regulatory processes, which may represent a potential pathogenesis of calculous cholecystitis. Then, we identified transcription factors (TFs) (including E2F1, MYC and NFKB1, etc.) and ncRNAs (including CRNDE, miR-590 and miR-340, etc.) that have potentially important regulatory effects on calculous cholecystitis. These pivot regulators may manipulate genes in modules to mediate the occurrence of calculous cholecystitis. In addition, we used drugtarget information to predict potential drugs for calculous cholecystitis, including Copper, Amitriptyline, Nortriptyline, and so on. These drugs may have certain pharmacological or toxicological effects on calculous cholecystitis, which requires further experimental exploration. Overall, based on a comprehensive functional module’s analysis, we identified tissue-specific expression proteins, interactors and pivot regulators to analyze the underlying pathogenesis of calculous cholecystitis. The regulation of potential drugs also provided a valuable reference for drug developers to conduct drug relocation studies.
Keywords
Gallbladder calculus, Cholecystitis, Regulators, Dysfunctional modules, Potential drugs.