Investigation of the Genome-Wide Genetic and Epigenetic Networks for Drug Discovery Based on Systems Biology Approaches in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. The mechanisms leading to the progression of CRC are involved in both genetic and epigenetic regulations. In this study, we applied systems biology methods to identify potential biomarkers and conduct drug discovery in a computational approach. Using big database mining, we constructed a candidate protein-protein interaction network and a candidate gene regulatory network, combining them into a genome-wide genetic and epigenetic network (GWGEN). With the assistance of system identification and model selection approaches, we obtain real GWGENs for early-stage, mid-stage, and late-stage CRC. Subsequently, we extracted core GWGENs for each stage of CRC from their real GWGENs through a principal network projection method, and projected them to the Kyoto Encyclopedia of Genes and Genomes pathways for further analysis. Finally, we compared these core pathways resulting in different molecular mechanisms in each stage of CRC and identified carcinogenic biomarkers for the design of multiple-molecule drugs to prevent the progression of CRC. Based on the identified gene expression signatures, we suggested potential compounds combined with known CRC drugs to prevent the progression of CRC with querying Connectivity Map (CMap).

A Correlation Study of Prognostic Risk Prediction for Colorectal Cancer Based on Autophagy Signature Genes

“…Currently, targeted therapy is a new approach in the treatment of colorectal cancer and has been successful in prolonging the overall survival of CRC patients ( 1 ). And in the direction of molecular targeting, the development of potential biomarkers not only improves the early detection rate of CRC, but is also necessary for the development of drugs that can improve patient survival ( 9 , 10 ). Autophagy has been found to play an important role in cancer development and has been explored as a potential therapeutic target in a variety of malignancies ( 11 ).…”

Tumor-Derived Exosomes Enriched by miRNA-124 Promote Anti-tumor Immune Response in CT-26 Tumor-Bearing Mice

“…Consequently, it represents a critical health burden. Most investigations on CRC have focused on genetic and epigenetic alterations in protein-coding genes for their important function in CRC etiopathogenesis ( 2 , 3 ). However, microRNAs as a class of small non-coding RNAs have attracted much attention ( 4 ).…”

Perspective of Human Condensins Involved in Colorectal Cancer

“…Recently, all eight human condensin subunits have been found abnormally expressed in colorectal cancer and they are expected to become potential biomarkers and therapeutic targets for colorectal cancer in the future (Dávalos et al, 2012;Shiheido et al, 2012;Tokunaga et al, 2013;Feng et al, 2014;Je et al, 2014;Jinushi et al, 2014;Yin et al, 2017;Baergen et al, 2019;Montero et al, 2020;Yeh et al, 2020). Therefore, based on the brief introduction of the discovery and composition of human Abbreviations: CRC, colorectal cancer; SMC, structure maintenance of chromoses; hCAP, human chromosome associate polypeptide; NCAP, non-SMC condensin I complex subunit; MSI-H, high microsatellite instability; GRID2, glutamate ionotropic receptor delta type subunit 2; CBLN1, cerebellin 1 precursor; POU2F1, TF POU class 2 homeobox 1; HPGDS, hematopoietic prostaglandin D synthase.…”

“…Recently, all eight human condensin subunits have been found abnormally expressed in colorectal cancer and they are expected to become potential biomarkers and therapeutic targets for colorectal cancer in the future ( Dávalos et al, 2012 ; Shiheido et al, 2012 ; Tokunaga et al, 2013 ; Feng et al, 2014 ; Je et al, 2014 ; Jinushi et al, 2014 ; Yin et al, 2017 ; Baergen et al, 2019 ; Montero et al, 2020 ; Yeh et al, 2020 ). Therefore, based on the brief introduction of the discovery and composition of human condensins, this paper reviews the research progress and application perspective of all eight human condensin subunits in colorectal cancer to offer beneficial reference for related research.…”