Unveiling Racial Disparities in Localized Prostate Cancer: A Systems-Level Exploration of the lncRNA Landscape.

IF 2.8 3区 生物学 Q2 GENETICS & HEREDITY Genes Pub Date : 2025-02-17 DOI:10.3390/genes16020229
Rebecca A Morgan, E Starr Hazard, Stephen J Savage, Chanita Hughes Halbert, Sebastiano Gattoni-Celli, Gary Hardiman
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Abstract

Background/objectives: Prostate cancer (PC) is the most common non-cutaneous cancer in men globally, and one which displays significant racial disparities. Men of African descent (AF) are more likely to develop PC and face higher mortality compared to men of European descent (EU). The biological mechanisms underlying these differences remain unclear. Long non-coding RNAs (lncRNAs), recognized as key regulators of gene expression and immune processes, have emerged as potential contributors to these disparities. This study aimed to investigate the regulatory role of lncRNAs in localized PC in AF men relative to those of EU and assess their involvement in immune response and inflammation.

Methods: A systems biology approach was employed to analyze differentially expressed (DE) lncRNAs and their roles in prostate cancer (PC). Immune-related pathways were investigated through over-representation analysis of lncRNA-mRNA networks. The study also examined the effects of vitamin D supplementation on lncRNA expression in African descent (AF) PC patients, highlighting their potential regulatory roles in immune response and inflammation.

Results: Key lncRNAs specific to AF men were identified, with several being implicated for immune response and inflammatory processes. Notably, 10 out of the top 11 ranked lncRNAs demonstrated strong interactions with immune-related genes. Pathway analysis revealed their regulatory influence on antigen processing and presentation, chemokine signaling, and ribosome pathways, suggesting their critical roles in immune regulation.

Conclusions: These findings highlight the pivotal role of lncRNAs in PC racial disparities, particularly through immune modulation. The identified lncRNAs may serve as potential biomarkers or therapeutic targets to address racial disparities in PC outcomes.

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揭示局部前列腺癌的种族差异:lncRNA景观的系统级探索。
背景/目的:前列腺癌(PC)是全球男性中最常见的非皮肤癌症,并且表现出明显的种族差异。与欧洲人后裔相比,非洲人后裔(AF)更有可能发展为PC,并且面临更高的死亡率。这些差异背后的生物学机制尚不清楚。长链非编码rna (lncRNAs)被认为是基因表达和免疫过程的关键调节因子,已成为造成这些差异的潜在因素。本研究旨在探讨lncrna相对于EU在房颤男性局部PC中的调节作用,并评估其在免疫反应和炎症中的参与。方法:采用系统生物学方法分析差异表达(DE) lncrna及其在前列腺癌(PC)中的作用。通过lncRNA-mRNA网络的过代表性分析来研究免疫相关途径。该研究还检测了补充维生素D对非洲人后裔(AF) PC患者lncRNA表达的影响,强调了它们在免疫反应和炎症中的潜在调节作用。结果:鉴定出AF男性特异性的关键lncrna,其中一些与免疫反应和炎症过程有关。值得注意的是,排名前11位的lncrna中有10个表现出与免疫相关基因的强相互作用。通路分析揭示了它们对抗原加工和递呈、趋化因子信号传导和核糖体通路的调节作用,表明它们在免疫调节中起关键作用。结论:这些发现强调了lncrna在PC种族差异中的关键作用,特别是通过免疫调节。鉴定的lncrna可能作为潜在的生物标志物或治疗靶点,以解决种族差异的PC结果。
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来源期刊
Genes
Genes GENETICS & HEREDITY-
CiteScore
5.20
自引率
5.70%
发文量
1975
审稿时长
22.94 days
期刊介绍: Genes (ISSN 2073-4425) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to genes, genetics and genomics. It publishes reviews, research articles, communications and technical notes. There is no restriction on the length of the papers and we encourage scientists to publish their results in as much detail as possible.
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