Analyzing the regulation of miRNAs on protein-protein interaction network in Hodgkin lymphoma

Abstract

Background Hodgkin Lymphoma (HL) is a type of aggressive malignancy in lymphoma that has high incidence in young adults and elderly patients. Identification of reliable diagnostic markers and efficient therapeutic targets are especially important for the diagnosis and treatment of HL. Although many HL-related molecules have been identified, our understanding on the molecular mechanisms underlying the disease is still far from complete due to its complex and heterogeneous characteristics. In such situation, exploring the molecular mechanisms underlying HL via systems biology approaches provides a promising option. In this study, we try to elucidate the molecular mechanisms related to the disease and identify potential pharmaceutical targets from a network-based perspective. Results We constructed a series of network models. Based on the analysis of these networks, we attempted to identify the biomarkers and elucidate the molecular mechanisms underlying HL. Initially, we built three different but related protein networks, i.e., background network, HL-basic network and HL-specific network. By analyzing these three networks, we investigated the connection characteristic of the HL-related proteins. Subsequently, we explored the miRNA regulation on HL-specific network and analyzed three kinds of simple regulation patterns, i.e., co-regulation of protein pairs, as well as the direct and indirect regulation of triple proteins. Finally, we constructed a simplified protein network combined with the regulation of miRNAs on proteins to better understand the relation between HL-related proteins and miRNAs. Conclusions We find that the HL-related proteins are more likely to connect with each other compared to other proteins. Moreover, the HL-specific network can be further divided into five sub-networks and 49 proteins as the backbone of HL-specific network make up and connect these 5 sub-networks. Thus, they may be closely associated with HL. In addition, we find that the co-regulation of protein pairs is the main regulatory pattern of miRNAs on the protein network in the HL-specific network. According to the regulation of miRNA on protein network, we have identified 5 core miRNAs as the potential biomarkers for diagnostic of HL. Finally, several protein pathways have been identified to closely associated with HL, which provides deep insights into underlying mechanism of HL. Electronic supplementary material The online version of this article (10.1186/s12859-019-3041-9) contains supplementary material, which is available to authorized users.

Integrated Bioinformatics Analysis Deciphering the microRNA Regulation in Protein-Protein Interaction Network in Lung Adenocarcinoma

“…However, in reality, PPI network has dynamic property, which is intrinsically regulated by complex cellular mechanisms through time and space (Liang and Li 2007). Recent studies showed the significance of the miRNA regulation on protein-protein interaction networks (Rahimpour et al 2022;Du et al 2019;Lei et al 2019;Liang and Li 2007). Moreover, different methods have been developed to predict miRNA targets accurately at the genomic level (John et al 2004;Lewis et al 2003).…”