A Systems Biology Approach for Investigating Significant Biomarkers and Drug Targets Common Among Patients with Gonorrhea, Chlamydia, and Prostate Cancer: A Pilot Study.

IF 2.3 Q3 BIOCHEMICAL RESEARCH METHODS
Bioinformatics and Biology Insights Pub Date : 2023-11-27 eCollection Date: 2023-01-01 DOI:10.1177/11779322231214445
Abdulla Al Noman, Md Kobirul Islam, Tasmiah Feroz, Md Monir Hossain, Md Shahariar Kabir Shakil
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引用次数: 0

Abstract

Having a previous history of sexually transmitted diseases (STDs) such as gonorrhea and chlamydia increases the chance of developing prostate cancer, the second most frequent malignant cancer among men. However, the molecular functions that cause the development of prostate cancer in persons with gonorrhea and chlamydia are yet unknown. In this study, we studied RNA-seq gene expression profiles using computational biology methods to find out potential biomarkers that could help us in understanding the patho-biological mechanisms of gonorrhea, chlamydia, and prostate cancer. Using statistical methods on the Gene Expression Omnibus (GEO) data sets, it was found that a total of 22 distinct differentially expressed genes were shared among these 3 diseases of which 14 were up-regulated (PGRMC1, TSC22D1, SH3BGRL, NNT, CTSC, FRMD3, CCR2, FAM210B, VCL, PTGS1, SLFN11, SLC40A1, PROS1, and DSE) and the remaining 8 genes were down-regulated (PRNP, HINT3, MARCKSL1, TMED10, SH3KBP1, ENSA, DERL1, and KMT2B). Investigation on these 22 unique dysregulated genes using Gene Ontology, BioCarta, KEGG, and Reactome revealed multiple altered molecular pathways, including regulation of amyloid precursor protein catabolic process, ferroptosis, effects on gene expression of Homo sapiens PPAR pathway, and innate immune system R-HSA-168249. Four significant hub proteins namely VCL, SH3KBP1, PRNP, and PGRMC1 were revealed by protein-protein interaction network analysis. By analyzing gene-transcription factors and gene-miRNAs interactions, significant transcription factors (POU2F2, POU2F1, GATA6, and HIVEP1) and posttranscriptional regulator microRNAs (hsa-miR-7-5p) were also identified. Three potential therapeutic compounds namely INCB3284, CCX915, and MLN-1202 were found to interact with up-regulated protein C-C chemokine receptor type 2 (CCR2) in protein-drug interaction analysis. The proposed biomarkers and therapeutic potential molecules could be investigated for potential pharmacological targets and activity in the fight against in patients with gonorrhea, chlamydia, and prostate cancer.

研究淋病、衣原体和前列腺癌患者中常见的重要生物标志物和药物靶点的系统生物学方法:一项试点研究。
有过淋病和衣原体等性传播疾病的病史会增加患前列腺癌的几率,前列腺癌是男性中第二常见的恶性癌症。然而,导致淋病和衣原体患者前列腺癌发展的分子功能尚不清楚。在这项研究中,我们使用计算生物学方法研究RNA-seq基因表达谱,以寻找可能帮助我们理解淋病、衣原体和前列腺癌的病理生物学机制的潜在生物标志物。对GEO数据集进行统计学分析,发现3种疾病共有22个显著差异表达基因,其中上调14个(PGRMC1、TSC22D1、SH3BGRL、NNT、CTSC、FRMD3、CCR2、FAM210B、VCL、PTGS1、SLFN11、SLC40A1、PROS1、DSE),下调8个(PRNP、HINT3、MARCKSL1、TMED10、SH3KBP1、ENSA、DERL1、KMT2B)。利用Gene Ontology、BioCarta、KEGG和Reactome对这22个独特的失调基因进行研究,揭示了多种改变的分子途径,包括淀粉样蛋白前体蛋白分解代谢过程的调节、铁死亡、对智人PPAR途径基因表达的影响以及先天免疫系统R-HSA-168249。通过蛋白相互作用网络分析,发现了VCL、SH3KBP1、PRNP和PGRMC1四个重要枢纽蛋白。通过分析基因-转录因子和基因- mirna相互作用,还鉴定了显著转录因子(POU2F2、POU2F1、GATA6和HIVEP1)和转录后调节因子(hsa-miR-7-5p)。在蛋白-药物相互作用分析中,发现三种潜在的治疗化合物INCB3284、CCX915和MLN-1202与上调的蛋白C-C趋化因子受体2 (CCR2)相互作用。提出的生物标志物和潜在的治疗分子可用于研究潜在的药理学靶点和治疗淋病、衣原体和前列腺癌的活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bioinformatics and Biology Insights
Bioinformatics and Biology Insights BIOCHEMICAL RESEARCH METHODS-
CiteScore
6.80
自引率
1.70%
发文量
36
审稿时长
8 weeks
期刊介绍: Bioinformatics and Biology Insights is an open access, peer-reviewed journal that considers articles on bioinformatics methods and their applications which must pertain to biological insights. All papers should be easily amenable to biologists and as such help bridge the gap between theories and applications.
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