A Prospective to Regulatory Role of miRNAs on Wnt/β-catenin Signaling and Its Crosstalk to the Other Cellular Pathways in Tumorigenesis of Glioblastoma by a Systems Biology Approach

Abstract

Background: The Wnt plays a crucial role in the initiation, progression, and spread of glioblastoma (GBM). Recently, microRNAs (miRNAs) have been demonstrated to be key players in controlling cell growth and tumor formation. Objectives: The present study offers the latest insight into miRNAs that influence the Wnt pathway and their interaction with protein-coding genes. Methods: Previous studies on the regulatory function of miRNAs targeting the Wnt/catenin pathway were reviewed, and all miRNA-targeted genes were found in the miRDB database. Protein-protein interactions (PPIs) of miRNA-targeted genes were investigated using String and Cytoscape software, and hub proteins were examined. Gene-subnetwork Gene Ontology (GO) analysis was performed. Results: At first, 13 downregulated and 25 upregulated miRNAs targeting the Wnt pathway were obtained, each targeting 1,685 and 1,313 genes, respectively; 12 and 15 hub proteins were found in dysregulated miRNA-targeted genes, which interacted with most genes. The PPI network analysis and subnetwork GO analysis showed these proteins cross-talk with many other proteins that have key roles in the pathways that cause proliferation and malignancy in cells. Conclusions: Hub proteins are oncogenic proteins that increase gene replication and suppress apoptotic pathways, or tumor suppressors that prevent cancer. By focusing on hub proteins alone or as part of a multi-target approach, it is possible to treat GBM tumors successfully.