Integrated Network Analysis of microRNAs, mRNAs, and Proteins Reveals the Regulatory Interaction between hsa-mir-200b and CFL2 Associated with Advanced Stage and Poor Prognosis in Patients with Intestinal Gastric Cancer

Intestinal gastric cancer (IGC) carcinogenesis results from a complex interplay between environmental and molecular factors, ultimately contributing to disease development. We used integrative bioinformatic analysis to investigate IGC high-throughput molecular data to uncover interactions among diff...

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Bibliographic Details
Published in:Cancers 2023-11, Vol.15 (22), p.5374
Main Authors: dos Santos, Everton Cruz, Rohan, Paulo, Binato, Renata, Abdelhay, Eliana
Format: Article
Language:English
Subjects:
Apoptosis
Biomarkers
Cancer
Cancer patients
Carcinogenesis
Cell cycle
Cell death
Development and progression
Gastric cancer
Gene expression
Gene regulation
Genes
Genomes
Health savings accounts
Immune response
Intestine
Medical prognosis
Messenger RNA
MicroRNA
MicroRNAs
miRNA
mRNA
Patients
Performance evaluation
Proteins
Software
Stem cells
Stomach cancer
Survival analysis
Tumors
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Summary:Intestinal gastric cancer (IGC) carcinogenesis results from a complex interplay between environmental and molecular factors, ultimately contributing to disease development. We used integrative bioinformatic analysis to investigate IGC high-throughput molecular data to uncover interactions among differentially expressed genes, microRNAs, and proteins and their roles in IGC. An integrated network was generated based on experimentally validated microRNA-gene/protein interaction data, with three regulatory circuits involved in a complex network contributing to IGC progression. Key regulators were determined, including 23 microRNA and 15 gene/protein hubs. The regulatory circuit networks were associated with hallmarks of cancer, e.g., cell death, apoptosis and the cell cycle, the immune response, and epithelial-to-mesenchymal transition, indicating that different mechanisms of gene regulation impact similar biological functions. Altered expression of hubs was related to the clinicopathological characteristics of IGC patients and showed good performance in discriminating tumors from adjacent nontumor tissues and in relation to T stage and overall survival (OS). Interestingly, expression of upregulated hub hsa-mir-200b and its downregulated target hub gene/protein CFL2 were related not only to pathological T staging and OS but also to changes during IGC carcinogenesis. Our study suggests that regulation of CFL2 by hsa-miR-200b is a dynamic process during tumor progression and that this control plays essential roles in IGC development. Overall, the results indicate that this regulatory interaction is an important component in IGC pathogenesis. Also, we identified a novel molecular interplay between microRNAs, proteins, and genes associated with IGC in a complex biological network and the hubs closely related to IGC carcinogenesis as potential biomarkers.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15225374