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良性前列腺增生中差异表达基因的蛋白质-蛋白质相互作用网络的计算分析

Computational analysis of protein-protein interaction network of differentially expressed genes in benign prostatic hyperplasia.

作者信息

Sachdeva Ruchi, Kaur Navneet, Kapoor Paras, Singla Pooja, Thakur Nidhi, Singhmar Sakshi

机构信息

Department of Bioinformatics, Goswami Ganesh Dutta Sanatan Dharma College, Sector-32C, Chandigarh, India.

出版信息

Mol Biol Res Commun. 2022 Jun;11(2):85-96. doi: 10.22099/mbrc.2022.43721.1746.

DOI:10.22099/mbrc.2022.43721.1746
PMID:36059933
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9336786/
Abstract

Benign prostatic hyperplasia (BPH) is a commonly occurring disease in aging men. It involves cellular proliferation of stromal and glandular tissues leading to prostate enlargement. Current drug therapies show several adverse effects such as sexual dysfunctions and cardiovascular side effects. Therefore, there is a need to develop more effective medical treatment for BPH. In this regard, we aimed to identify genes which play a critical role in BPH. We have obtained the dataset of differentially expressed genes (DEGs) of BPH from NCBI GEO. DEGs were investigated in the context of their protein-protein interactions (PPI). Hub genes i.e. genes associated with BPH were scrutinized based on the topological parameters of the PPI network. These were analyzed for functional annotations, pathway enrichment analysis and transcriptional regulation. In total, 38 hub genes were identified. Hub genes such as transcription factor activator protein-1 and adiponectin were found to play key roles in cellular proliferation and inflammation. Another gene peroxisome proliferator activated receptor gamma was suggested to cause obesity, a common comorbidity of BPH. Moreover, our results indicated an important role of transforming growth factor-beta (TGF-β) signaling and smooth muscle cell proliferation which may be responsible for prostate overgrowth and associated lower urinary tract symptoms frequently encountered in BPH patients. Zinc finger protein Snai1 was the most prominent transcription factor regulating the expression of hub genes that participate in TGF-β signaling. Overall, our study has revealed significant hub genes that can be employed as drug targets to develop potential therapeutic interventions to treat BPH.

摘要

良性前列腺增生(BPH)是老年男性中常见的疾病。它涉及基质和腺组织的细胞增殖,导致前列腺肿大。目前的药物治疗显示出多种不良反应,如性功能障碍和心血管副作用。因此,需要开发更有效的BPH治疗方法。在这方面,我们旨在鉴定在BPH中起关键作用的基因。我们从NCBI基因表达综合数据库(GEO)获得了BPH的差异表达基因(DEG)数据集。在蛋白质-蛋白质相互作用(PPI)的背景下研究了DEG。基于PPI网络的拓扑参数仔细审查了枢纽基因,即与BPH相关的基因。对这些基因进行了功能注释、通路富集分析和转录调控分析。总共鉴定出38个枢纽基因。发现转录因子激活蛋白-1和脂联素等枢纽基因在细胞增殖和炎症中起关键作用。另一个基因过氧化物酶体增殖物激活受体γ被认为会导致肥胖,这是BPH常见的合并症。此外,我们的结果表明转化生长因子-β(TGF-β)信号传导和平滑肌细胞增殖的重要作用,这可能是BPH患者中常见的前列腺过度生长和相关下尿路症状的原因。锌指蛋白Snai1是调节参与TGF-β信号传导的枢纽基因表达的最突出转录因子。总体而言,我们的研究揭示了重要的枢纽基因,这些基因可作为药物靶点,以开发潜在的治疗干预措施来治疗BPH。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4779/9336786/c9b1c05a358c/mbrc-11-85-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4779/9336786/2d4c28c84fb9/mbrc-11-85-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4779/9336786/78a816c721e1/mbrc-11-85-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4779/9336786/c9b1c05a358c/mbrc-11-85-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4779/9336786/2d4c28c84fb9/mbrc-11-85-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4779/9336786/78a816c721e1/mbrc-11-85-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4779/9336786/c9b1c05a358c/mbrc-11-85-g003.jpg

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