Deciphering the Regulatory Symphony: MicroRNA Orchestration of the RAS/MAPK Signaling Pathway and its Interplay across Cellular Networks in Colorectal Cancer Tumorigenesis – A Systems Biology Perspective

سال انتشار: 1402
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 115

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شناسه ملی سند علمی:

IBIS12_084

تاریخ نمایه سازی: 12 آبان 1403

چکیده مقاله:

Background: Colorectal cancer (CRC) stands as a global health challenge, prompting anexploration of its molecular intricacies. The RAS/MAP kinase pathway, pivotal in cancer development,intertwines with microRNAs (miRNAs), shaping CRC's dynamic cellular landscape. This study utilizesa systems biology approach, employing advanced bioinformatics tools to unravel miRNA-mediatedregulatory networks in CRC. Investigating miRNA dysregulation, identifying hub genes, and exploringinterplay between signaling pathways aim to provide nuanced insights into CRC's molecular landscape.Protein-protein network analysis uncovers the interconnected web of miRNA-targeted genes within theRAS/MAPK signaling pathway. Utilizing STRING and Cytoscape, we pinpoint ۱۳ hub proteinsorchestrating network dynamics. GO and KEGG enrichment analyses reveal intricate regulatorymechanisms. Cluster analysis unveils ۸۱۷ clusters, emphasizing CRC significance. Hub gene promotermotif analysis delves into transcriptional regulatory elements governing CRC pathogenesis.Dysregulated miRNA expression in CRC is explored, emphasizing miRNAs' dual roles as oncogenesor tumor suppressors. A comprehensive list of miRNAs targeting the RAS/MAPK pathway in CRC ispresented. Protein-protein interaction networks highlight ۱۳ hub proteins, predominantly linked totranscriptional regulation. Enriched pathways, such as the MAPK cascade, underscore their pivotalroles. Cluster analysis reveals CRC's significance, emphasizing involvement in glucose metabolism.Promoter motif analysis uncovers significant motifs targeted by dysregulated miRNAs. Transcriptionfactor 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 incancer development.This integrative study unravels the regulatory intricacies of miRNAs in the RAS/MAPK signalingpathway, shedding light on CRC's molecular landscape. Identification of hub genes, enriched pathways,and regulatory motifs provides valuable insights for diagnostics and therapeutics, offering promisingtargets for simultaneous inhibition in cancer cell growth.

نویسندگان

Alireza Pasdar

Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Elnaz Farzadifar

Biology Department, Faculty of Sciences, Science and Arts University, Yazd, Iran