Aldakheel Fahad M, Alnajran Hadeel, Mateen Ayesha, Alduraywish Shatha A, Alqahtani Mohammed S, Syed Rabbani
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Saudi Arabia.
Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Sci Rep. 2025 Jan 29;15(1):3646. doi: 10.1038/s41598-025-85502-4.
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.
前列腺癌是一个重大的健康问题，其进展受复杂分子因素的影响。值得注意的是，miRNA与转录组模式变化之间的相互作用尚未完全明确。我们的研究旨在填补这一知识空白，运用计算技术探索miRNA和转录组改变如何共同调节前列腺癌的发展。该研究涉及从特定于前列腺癌的GEO数据库中检索miRNA表达数据。使用R语言中的“limma”软件包进行差异表达miRNA（DEM）的鉴定。利用MiRTarBase数据库将这些DEM与mRNA相互作用进行整合。最后，使用Cytoscape软件构建描绘miRNA-mRNA相互作用的网络，以分析前列腺癌的调控网络。该研究确定了前列腺癌中七个关键的差异表达微小RNA（DEmiRNA）：hsa-miR-185-5p、hsa-miR-153-3p、hsa-miR-198、hsa-miR-182-5p、hsa-miR-223-3p、hsa-miR-372-3p和hsa-miR-188-5p。这些miRNA影响关键基因，包括FOXO3、NFAT3、PTEN、RHOA、VEGFA,、SMAD7和CDK2，它们在肿瘤抑制和肿瘤发生中都发挥着重要作用。分析揭示了一个复杂的miRNA-mRNA相互作用网络，包含1849个节点和3604条边。通过ClueGO进行的功能富集分析突出了与这些mRNA靶标相关的74个基因本体（GO）术语。该分析揭示了它们对关键生物学过程和分子功能的重大影响，如细胞周期蛋白依赖性蛋白激酶活性、有丝分裂DNA损伤检查点信号传导、应激激活的丝裂原活化蛋白激酶级联反应、外在凋亡信号通路的调节以及细胞黏附的正调控。我们对miRNA和差异表达基因（DEG）的分析揭示了前列腺癌发展中既有已确定的调节因子，也有潜在的新调节因子的有趣组合。这些发现既强化了我们目前对前列腺癌分子格局的理解，也指出了可能通向新治疗策略的未探索途径。通过绘制这些调控关系，我们的工作为开发更具针对性和有效性的治疗方法所需的不断增长的知识库做出了贡献。
