Journal of Cell Signaling
Open Access

Abstract

MicroRNA Regulation of RAS/MAPK Pathway: Unveiling Interactions in Colorectal Cancer Tumorigenesis and Beyond

Alireza Pasdar1, Pouria Abidi2, Farzad Rahmani2, Elnaz Farzadifar3, Forouzan Amerizadeh4,5*

The Rat Sarcoma virus/Mitogen Activated Protein Kinase (RAS/MAPK) pathway, pivotal in cancer development, intertwines with microRNAs (miRNAs), shaping Colorectal Cancers (CRCs) dynamic cellular landscape. This study utilizes a systems biology approach, employing advanced bioinformatics tools to unravel miRNA-mediated regulatory networks in CRC. Investigating miRNA dysregulation, identifying hub genes and exploring interplay between signalling pathways aim to provide nuanced insights into CRCs molecular landscape. Protein-protein network analysis uncovers the interconnected web of miRNA-targeted genes within the RAS/MAPK signaling pathway. Utilizing STRING and Cytoscape, we pinpoint 13 hub proteins orchestrating network dynamics. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses reveal complex regulatory mechanisms. Cluster analysis unveils 817 clusters, emphasizing CRC significance. Hub gene promoter motif analysis delves into transcriptional regulatory elements governing CRC pathogenesis. A comprehensive list of miRNAs targeting the Phosphatidylinositol 3-Kinase (PI3K) pathway in CRC is presented. Protein-protein interaction networks highlight 13 hub proteins, predominantly linked to transcriptional regulation. Enriched pathways, such as the MAPK cascade, underscore their pivotal roles. Cluster analysis reveals CRCs significance, emphasizing involvement in glucose metabolism. Promoter motif analysis uncovers significant motifs targeted by dysregulated miRNAs. Transcription factor motifs reveal biological roles, with implications in signal transduction and cell proliferation. Enrichment in nucleus-based terms and disruption of cell polarity underscore potential implications in cancer development. This integrative study resolves the regulatory complex of miRNAs in the RAS/MAPK signaling pathway, explaining on CRCs molecular landscape. Identification of hub genes, enriched pathways and regulatory motifs provides valuable insights for diagnostics and therapeutics, offering potential targets for simultaneous inhibition in cancer cell growth.

Published Date: 2024-10-03; Received Date: 2024-09-02