Comprehensive computational analysis of differentially expressed miRNAs and their influence on transcriptomic signatures in prostate cancer

Abstract Prostate cancer presents a major health issue, with its progression influenced by intricate molecular factors. Notably, the interplay between miRNAs and changes in transcriptomic patterns is not fully understood. Our study seeks to bridge this knowledge gap, employing computational techniqu...

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Main Authors: Fahad M. Aldakheel, Hadeel Alnajran, Ayesha Mateen, Shatha A. Alduraywish, Mohammed S. Alqahtani, Rabbani Syed
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-85502-4
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author Fahad M. Aldakheel
Hadeel Alnajran
Ayesha Mateen
Shatha A. Alduraywish
Mohammed S. Alqahtani
Rabbani Syed
author_facet Fahad M. Aldakheel
Hadeel Alnajran
Ayesha Mateen
Shatha A. Alduraywish
Mohammed S. Alqahtani
Rabbani Syed
author_sort Fahad M. Aldakheel
collection DOAJ
description Abstract Prostate cancer presents a major health issue, with its progression influenced by intricate molecular factors. Notably, the interplay between miRNAs and changes in transcriptomic patterns is not fully understood. Our study seeks to bridge this knowledge gap, employing computational techniques to explore how miRNAs and transcriptomic alterations jointly regulate the development of prostate cancer. The study involved retrieving miRNA expression data from the GEO database specific to prostate cancer. Identification of DEMs was conducted using the ‘limma’ package in R. Integration of these DEMs with mRNA interactions was done using the MiRTarBase database. Finally, a network depicting miRNA-mRNA interactions was constructed using Cytoscape software to analyze the regulatory network of prostate cancer. The study pinpointed seven pivotal differentially expressed microRNAs (DEmiRNAs) in prostate cancer: hsa-miR-185-5p, hsa-miR-153-3p, hsa-miR-198, hsa-miR-182-5p, hsa-miR-223-3p, hsa-miR-372-3p, and hsa-miR-188-5p. These miRNAs influence key genes, including FOXO3, NFAT3, PTEN, RHOA, VEGFA, SMAD7, and CDK2, playing significant roles in both tumor suppression and oncogenesis. The analysis revealed a complex network of miRNA-mRNA interactions, comprising 1849 nodes and 3604 edges. Functional Enrichment Analysis through ClueGO highlighted 74 GO terms associated with these mRNA targets. This analysis uncovered their substantial impact on critical biological processes and molecular functions, such as cyclin-dependent protein kinase activity, mitotic DNA damage checkpoint signalling, stress-activated MAPK cascade, regulation of extrinsic apoptotic signalling pathway, and positive regulation of cell adhesion. Our analysis of miRNAs and DEGs genes revealed an intriguing mix of established and potentially novel regulators in prostate cancer development. These findings both reinforce our current understanding of prostate cancer’s molecular landscape and point to unexplored pathways that could lead to novel therapeutic strategies. By mapping these regulatory relationships, our work contributes to the growing knowledge base needed for developing more targeted and effective treatments.
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spelling doaj-art-f3cdc94ae5ea4c16ae780a6434f33c932025-02-02T12:24:48ZengNature PortfolioScientific Reports2045-23222025-01-011511910.1038/s41598-025-85502-4Comprehensive computational analysis of differentially expressed miRNAs and their influence on transcriptomic signatures in prostate cancerFahad M. Aldakheel0Hadeel Alnajran1Ayesha Mateen2Shatha A. Alduraywish3Mohammed S. Alqahtani4Rabbani Syed5Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud UniversityDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud UniversityDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud UniversityDepartment of Family and Community Medicine, College of Medicine, King Saud UniversityDepartment of Pharmaceutics, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutics, College of Pharmacy, King Saud UniversityAbstract Prostate cancer presents a major health issue, with its progression influenced by intricate molecular factors. Notably, the interplay between miRNAs and changes in transcriptomic patterns is not fully understood. Our study seeks to bridge this knowledge gap, employing computational techniques to explore how miRNAs and transcriptomic alterations jointly regulate the development of prostate cancer. The study involved retrieving miRNA expression data from the GEO database specific to prostate cancer. Identification of DEMs was conducted using the ‘limma’ package in R. Integration of these DEMs with mRNA interactions was done using the MiRTarBase database. Finally, a network depicting miRNA-mRNA interactions was constructed using Cytoscape software to analyze the regulatory network of prostate cancer. The study pinpointed seven pivotal differentially expressed microRNAs (DEmiRNAs) in prostate cancer: hsa-miR-185-5p, hsa-miR-153-3p, hsa-miR-198, hsa-miR-182-5p, hsa-miR-223-3p, hsa-miR-372-3p, and hsa-miR-188-5p. These miRNAs influence key genes, including FOXO3, NFAT3, PTEN, RHOA, VEGFA, SMAD7, and CDK2, playing significant roles in both tumor suppression and oncogenesis. The analysis revealed a complex network of miRNA-mRNA interactions, comprising 1849 nodes and 3604 edges. Functional Enrichment Analysis through ClueGO highlighted 74 GO terms associated with these mRNA targets. This analysis uncovered their substantial impact on critical biological processes and molecular functions, such as cyclin-dependent protein kinase activity, mitotic DNA damage checkpoint signalling, stress-activated MAPK cascade, regulation of extrinsic apoptotic signalling pathway, and positive regulation of cell adhesion. Our analysis of miRNAs and DEGs genes revealed an intriguing mix of established and potentially novel regulators in prostate cancer development. These findings both reinforce our current understanding of prostate cancer’s molecular landscape and point to unexplored pathways that could lead to novel therapeutic strategies. By mapping these regulatory relationships, our work contributes to the growing knowledge base needed for developing more targeted and effective treatments.https://doi.org/10.1038/s41598-025-85502-4Prostate cancermiRNAmRNA targetsHsa-miR-185-5pHsa-miR-153-3p
spellingShingle Fahad M. Aldakheel
Hadeel Alnajran
Ayesha Mateen
Shatha A. Alduraywish
Mohammed S. Alqahtani
Rabbani Syed
Comprehensive computational analysis of differentially expressed miRNAs and their influence on transcriptomic signatures in prostate cancer
Scientific Reports
Prostate cancer
miRNA
mRNA targets
Hsa-miR-185-5p
Hsa-miR-153-3p
title Comprehensive computational analysis of differentially expressed miRNAs and their influence on transcriptomic signatures in prostate cancer
title_full Comprehensive computational analysis of differentially expressed miRNAs and their influence on transcriptomic signatures in prostate cancer
title_fullStr Comprehensive computational analysis of differentially expressed miRNAs and their influence on transcriptomic signatures in prostate cancer
title_full_unstemmed Comprehensive computational analysis of differentially expressed miRNAs and their influence on transcriptomic signatures in prostate cancer
title_short Comprehensive computational analysis of differentially expressed miRNAs and their influence on transcriptomic signatures in prostate cancer
title_sort comprehensive computational analysis of differentially expressed mirnas and their influence on transcriptomic signatures in prostate cancer
topic Prostate cancer
miRNA
mRNA targets
Hsa-miR-185-5p
Hsa-miR-153-3p
url https://doi.org/10.1038/s41598-025-85502-4
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