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Mitogen-Activated Protein Kinase Pathway and Four Genes Involved in the Development of Benign Prostatic Hyperplasia: In Vivo and Vitro Validation
29 Pages Posted: 31 Mar 2022
More...Abstract
Background: Benign prostatic hyperplasia (BPH) is a common disease in elderly males, but its pathogenesis remains unclear. The aim of this study was to profile the proteome of the BPH rat prostates, human prostate tissues, and human cell lines for signaling changes and biomarker signatures.
Methods: We used data independent acquisition mass spectrometry to perform a quantitative proteomics analysis in 7 Rats samples, 4 with normal prostate and 3 with BPH. The proteins including Glutaminyl-peptide cyclotransferase (QPCT), Rho guanine nucleotide exchange factor 37 (ARHGEF37), Filamin-C (FLNC), Galectin-7 (LGALS7) are significantly upregulated and top 10 upregulated proteins. The differentially expressed proteins (DEPs) and protein-coding genes which could be the potential therapeutic target were investigated. qPCR was used to validate the expression of DEPs in rat prostate tissues and human cell lines including BPH-1 and WPMY-1. Additionally, the gene expression profiling datasets (GSE119195) of human tissues were obtained from Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) of the National Center for Biotechnology Information and the significant signaling pathway were found.
Findings: We identified 196 DEPs in BPH and sham rats and revealed DEGs found in human tissues were mainly clustered in MAPK signaling pathways. In addition, QPCT, ARHGEF37, FLNC, LGALS7 were up-regulated in BPH samples in vivo and in vitro.
Interpretation: This work finds that MAPK signaling pathways plays an important role in the development of BPH. QPCT, ARHGEF37, FLNC, LGALS7 could be significant biomarkers in BPH.
Funding Information: The study was supported by the Fundamental Research Funds for the Central Universities of Wuhan University (2042021kf1041). The funders did not act as a role in manuscript design, data collection, data analysis, interpretation nor writing of the manuscript.
Declaration of Interests: The authors have declared that no conflict of interest exists.
Ethics Approval Statement: All animal protocols were approved by the Institutional Animal Care and Use Committee (IACUC) of Wuhan University (IACUC animal approval protocol #2018119).
Keywords: benign prostatic hyperplasia, proteomics, MAPK pathway, genetic markers, genes
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