The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. The androgen-regulated TMPRSS2 promoters form a fusion gene with coding regions of the proto-oncogenic ETS transcription factor family members, which are closely related to prostate cancer and regulate many biological processes (Tomlins et al., 2005). In this review, we examine potential mechanisms that may explain why the sense of smell is lost or altered. The TMPRSS2: ERG fusion transcripts in urine samples were found to be one of the most advanced urine-based prostate cancer (PCa) early detection biomarkers. GENEMANIA can generate a list of genes with similar functions as a query and build an interactive functional association network to illustrate the relationship between genes and data sets. (2020). Zang et al, 2020. This site complies with the HONcode standard for trustworthy health information: verify here. Bookshelf The .gov means its official. Via GO and KEGG analyses of GSE30589 and GSE52920 in R, TMPRSS2 was further found to be involved in a variety of virus-related functions (Table 1) and multiple immune-related pathways (Table 2). Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected. Only bands not corresponding to the predicted size. (H) GSE23321 effector memory vs. nave cd8 t cell dn. J. Virol. J. Virol. This protein also facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins. Table 1. The ERG overexpression induced by TMPRSS2-ERG gene fusion contributes to the development of prostate cancer. (2001). ERG is a member of the ETS (erythroblast transformation-specific) family of transcription factors. Hoffmann et al, 2020. Androgen stimulation can increase expression of the TMPRSS2-ERG . As a serine protease, it is involved in the cleaving peptide bonds of proteins that have serine as the nucleophilic amino acid within the active site. Some studies have even shown SARS-CoV-2 RNA in stool samples of COVID-19 patients, although this does not necessarily mean the presence of infectious viruses being present in feces. Promoter methylation levels of TMPRSS2 in PRAD. GSE56677 and GSE52920 were both used to analyze the changes of TMPRSS2 expression in Vero E6 cells and mice lung after SARS-COV infection. (2011). Shabir, Osman. doi: 10.1016/j.cell.2020.02.052, Jimenez-Guardeno, J. M., Nieto-Torres, J. L., Dediego, M. L., Regla-Nava, J. The RNA data was used to cluster genes according to their expression across single cell types. on this website is designed to support, not to replace the relationship A., Alvarez, E., Oliveros, J. C., et al. In the past decade, several genes associated with prostate cancer have been identified. No use, distribution or reproduction is permitted which does not comply with these terms. RNA consistency i Medium consistency between antibody staining and RNA expression data. Normally, ERG is not regulated by androgens but after this oncogenic fusion, ERG regulation is henceforth controlled by androgens aggravating prostate cancer and promotion to metastasis. Natl. tmprss2-erg gene fusion was evaluated by fluorescence in situ hybridization (fish) using break-apart probes of the erg gene, as previously described. However, in VCaP ERG shRNA (low ERG) cells, enzalutamide did not inhibit the TMPRSS2 gene expression at 5 M concentration and all other genes were inhibited to a lower extent compared to ERG intact . Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. TMPRSS2 participated in the KEGG enrichment analysis results of GSE30589 and GSE56677. J. Clin. p < 0.001). Promoter methylation levels of TMPRSS2 were low in (AE). In addition, TMPRSS2 is a candidate proteolytic activated human influenza virus, which might play an important role in screening other progenitors in the future (Bttcher et al., 2006). Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity. Expression of the TMPRSS2: ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. doi: 10.1093/nar/gkq537, Wu, M., Wanggou, S., Li, X., Liu, Q., and Xie, Y. . TMPRSS2 and TMPRSS4 Promote SARS-CoV-2 Infection of Human Small Intestinal Enterocytes. BMC Genomics 15:1161. doi: 10.1186/1471-2164-15-1161, Smyth, G. K., Michaud, J., and Scott, H. S. J. Although common in hematologic and mesenchymal malignancies, recurrent gene fusions have not been well characterized in epithelial carcinomas. This database was used to investigate the gene expression of TMPRSS2 in the prostate gland (Lonsdale et al., 2013). TMPRSS2 is essential for the cell entry of influenza viruses and coronaviruses, including SARS-CoV, SARS-CoV-2 and MERS. Using the TIMER database,2 this study analyzed the expression of TMPRSS2 in PRAD patients and six types of infiltration of immune cells (B-cells, CD4+ T-cells, CD8+ T-cells, neutrophils, macrophages, and dendritic cells) using an abundance of correlation (Li et al., 2017). Cells were harvested at 0, 3, 7, 12, 18, and 24 h post-infection (hpi), RNA extracted, and transcriptomics analyzed by microarray (Selinger et al., 2014). More specifically, TMPRSS2 can cleave the SARS-COV-2 spike protein, facilitating viral entry and activation (Strope et al., 2020), and TMPRSS2-expressing cell lines are highly susceptible to SARS-COV, Middle East respiratory syndrome-coronavirus (MERS-COV), and SARS-COV-2 (Matsuyama et al., 2020), which prompted us to explore the association between TMPRSS2 and SARS-COV-2, especially in PRAD patients. (ACE2 and TMPRSS2). In addition, we studied the correlation of the level of immune infiltration and markers of immune cell type in the TIMER database, analyzed the prognosis based on the expression level of TMPRSS2 in the related immune cell subsets, and determined the methylation profile of TMPRSS2 promoter by UALCAN database. After correcting the tumor purity, the immune cell type markers in PRAD were further studied. The exact biological function of TMPRSS2 is largely unknown, although research has shown that it is involved in certain pathologies (outlined below). Progress in Molecular Biology and Translational Science 99:1-50, Stopsack et al, 2020. Find methods information, sources, references or conduct a literature review on GENE . TMPRSS2-ERG fusion is the most common known gene rearrangement in prostate carcinoma. A pathology atlas of the human cancer transcriptome. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. 2020). The results showed that prostate adenocarcinoma patients with a high level of TMPRSS2 expression, and Gleason score exhibited a longer survival period (Figure 4E). Animal studies have shown that healthy wild-type mice infected with SARS-CoV develop acute pneumonia and exhibit body weight loss of up to 15%, though non die as a result and show recovery. [17] The fact that TMPRSS2 has no known irreplaceable function makes it a promising target for preventing SARS-CoV-2 virus transmission. This study analyzed the changes of TMPRSS2 mRNA in PRAD via the Oncomine, TIMER and GEO databases and explored the correlation between TMPRSS2 and immune infiltration (Figure 12). (accessed December 11, 2022). Prostate cancer is very common in elderly men in developed countries. Bhowmick, N. A., Oft, J., Dorff, T., Pal, S., Agarwal, N., Figlin, R. A., et al. All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions. Viruses found to use this protein for cell entry include Influenza virus and the human coronaviruses HCoV-229E, MERS-CoV, SARS-CoV and SARS-CoV-2 (COVID-19 virus). Overexpression of mitochondrial serine hydroxyl-methyltransferase 2 is associated with poor prognosis and promotes cell proliferation and invasion in gliomas. Invest. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. 10:e1004320. Additionally, the correlation between TMPRSS2 and immune infiltration in PRAD was analyzed in the TIMER database and TISIDB database. doi: 10.1093/nar/gkx247, Tomlins, S. A., Rhodes, D. R., Perner, S., Dhanasekaran, S. M., Mehra, R., and Sun, X. W. (2005). ", "The pivotal role of TMPRSS2 in coronavirus disease 2019 and prostate cancer", "A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic", "Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2", 10.1002/1096-9896(2000)9999:9999<::AID-PATH743>3.0.CO;2-T, "Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia", "Cloning and characterization of the cDNA and gene for human epitheliasin", "The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells", "TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer", "Three-color FISH analysis of TMPRSS2/ERG fusions in prostate cancer indicates that genomic microdeletion of chromosome 21 is associated with rearrangement", "Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium", "TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions", "Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer", "Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues", https://en.wikipedia.org/w/index.php?title=TMPRSS2&oldid=1114113877, This page was last edited on 4 October 2022, at 21:48. This review focuses on the characteristics, oncogenic and rearranged mechanism, and clinical application of TMPRSS2-ETS gene fusions. TMPRSS2:ERG Gene Fusions in Prostate Cancer of West African Men and a Meta-Analysis of Racial Differences. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. Additionally, TMPRSS2 encodes an intracellular type II transmembrane protein, LDL receptor A (LDLRA), and the scavenger receptor cysteine-rich (SRCR) and serine protease domains (Vaarala et al., 2001). Serine proteases are known to be involved in many physiological and pathological processes. Linear univariate and multivariate regression models were built from TCGA HNSCC patients considering TMPRSS2 as outcome variable. The TMPRSS2-ERG Fusion FISH Probeis used to confirm a fusion of the TMPRSS2 and ERG genes. 45, 580585. 118 Articles, This article is part of the Research Topic, https://doi.org/10.3389/fgene.2020.575770, http://software.broadinstitute.org/gsea/index.jsp, Creative Commons Attribution License (CC BY). Immunohistochemistry (IHC) of TMPRSS2 expression in prostatic adenocarcinoma (PRAD) tissues and corresponding normal tissues based on the Human Protein Atlas (HPA). In addition, GSE56677 and GSE52920 were used to study the expression changes of TMPRSS2 in vivo and in vitro after SARS-COV infection. The expression of TMPRSS2 was detected in the Human Protein Atlas (HPA) database. However, SARS-CoV-2 can also be primed by CatB/L (endosomal cysteine protease) in addition to TMPRSS2, thus inhibition of both TMPRSS2 and CatB/L (by E-64d) would be the most robust approach to blocking viral entry through ACE2 receptors through blockage of TMPRSS2 may be sufficient in most cases. Iljin K, Wolf M, Edgren H, Gupta S, Kilpinen S, Skotheim RI, Peltola M, Smit F, Verhaegh G, Schalken J, Nees M, Kallioniemi O. Table 1 TMPRSS2 gene association with immune signature, MYC and MYC signature, HPV status and P53 mutation in HNSCC patients. The RNA data was used to cluster genes according to their expression across tissues. The Role of Digital Biomarkers in Psychiatry, How Veterinary Vaccines Affect Human Health, Discovery of biomarkers lays the groundwork for predicting preeclampsia, Strontium-loaded hydrogel scaffolds promote wound healing by stimulating gingival fibroblast activity, Structural studies pave the way for cancer drugs that could target only mutated versions, Researchers seek to reduce Chikungunya virus-caused joint pain with new drug, An epigenetic modification improves the defense against infections, research shows, Antalis et al, 2011. 5(47):eabc3582, Yoshikawa et al, 2019. A pneumonia outbreak associated with a new coronavirus of probable bat origin. J Virol. Correlation between TMPRSS2 expression and immune infiltration in PRAD in tumor immune assessment resource (TIMER) database. Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas. In general, TMPRSS2 primarily affects tumor metastasis by intervening in the signaling pathway, but the mechanism of its influence on the prognosis of PRAD is still unclear. Science 347:1260419. doi: 10.1126/science.1260419, Uhlen, M., Zhang, C., Lee, S., Sjstedt, E., Fagerberg, L., Bidkhori, G., et al. The important role of TMPRSS in regulating the virus suggests its potential association with immune cells in the tumor microenvironment. and c-Myc, as well as inhibiting key downstream genes, including PSA and TMPRSS2. The results showed that the expressions of TMPRSS2 in the control group was slightly decreased compared with the other group (Figure 11B), and mice lungs after SARS-COV infection obviously increased compared with the control group (Figure 11A). (B) GSE5589 wt vs. il6 ko lps stim macrophage 180 min dn. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. The methylation level of TMPRSS2 promoter in normal tissue was significantly higher than that in PRAD. Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells ( PubMed: 15537383, PubMed: 26018085, PubMed: 25122198 ). The RNA-seq expression data in tumors from the TCGA TIMER database (Figure 1D) show that TMPRSS2 displays obviously high expression in PRAD. ERG (ETS-related gene) is an oncogene. Sungnak and colleagues assessed the transcript expression of genes involved in the viral entry in healthy human donors using single-cell RNA sequencing, and they showed that ACE2 and COVID-19 and androgen targeted therapy for prostate cancer patients. CCS1477, a clinical candidate, causes complete tumour growth inhibition in a 22Rv1 xenograft model at doses which are well tolerated. . Image Credit: Kateryna Kon/Shutterstock.com. All brain expression profiles are based on data from HPA. (2017). Furthermore, rabbit raised sera against the S-domain of SARS reduced both SARS-CoV-S and SARS-CoV-2-S driven entry into cells. Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3. p < 0.001. The protein expression of TMPRSS2 was significantly reduced in normal tissue, and the protein level was significantly elevated in tumor tissue (Figures 2AD). Nat. TMPRSS2 (Transmembrane Serine Protease 2) is a Protein Coding gene. Further studies on immune cell type marker PRAD (Table 1) showed that the expression level of TMPRSS2 mRNA was correlated with B-cells (CD19, CD27, and CD38), and CD8+ in PRAD T-cells (CD8A and CD8B), neutrophil granulocytes (FCGR3B, SIGLEC5, and S100A12), macrophages (CD84 and CD163), Th1 (STAT4 and STAT1), Treg (STAT5B and TGFB1), and T-cell failure (PDCD1, CTLA4, LAG3, and GZMB) were significantly correlated, suggesting that these results strongly confirm the close correlation between TMPRSS2 and immune infiltration of PRAD. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. DNA methylation profiling in the clinic: applications and challenges. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. All genes with at least one predicted secreted isoform have been annotated and classified with the aim to determine if the corresponding protein(s) are: The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. Detection or not of the gene in blood, based on proximity extension assays (Olink) for a longitudinal wellness study covering 76 individuals with three visits during two years. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity. From the GTEx projects, we know that the TMPRSS2 gene is highly expressed in the prostate (Figure 1B). Afar, D. E. H., Vivanco, I., Hubert, R. S., Kuo, J., Chen, E. I., Saffran, D. C., et al. 13 the probes, consisting of a rhodamine-labeled 5- erg probe ( bac rp11-95i21) and a fluorescein isothiocyanate-labeled 3- erg probe ( bac rp11-476d17 ), were obtained from children's hospital of Genet. Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models. p < 0.01, and *** Prostate cancer is one of the leading causes of morbidity and mortality in men 50 years of age, whose incidence rate varies in different countries and ethnic groups (Parsons et al., 2001). Subsequently, we conducted a survival analysis and gene ontology (GO) pathway analysis in the TISID database and detected the expression of TMPRSS2 in the Human Protein Atlas (HPA) database. Intracellular, Membrane, Secreted (different isoforms), Cell type enhanced (Prostatic glandular cells, Distal enterocytes, Gastric mucus-secreting cells, Proximal enterocytes, Paneth cells), Prognostic marker in renal cancer (favorable) and endometrial cancer (favorable), Prostate cancer - Lipid metabolism (mainly), Plasma membrane-anchored serine protease that participates in proteolytic cascades of relevance for the normal physiolog, This gene encodes a protein that belongs to the serine protease family. Therefore, we used the UALCAN database to verify the methylation levels of TMPRSS2 promoter in PRAD. GSE52920 contains three biological sample types (SARS-COV-wt, SARS-COV-mutPBM, and Mock) based on mice lung tissue. We use cookies to enhance the usability of our website. Moreover, the UALCAN database was used to evaluate the effect of TMPRSS expression, molecular signature, race and Gleason score on PRAD patient survival. Clinical features of Middle East respiratory syndrome (MERS) include severe acute pneumonia and renal failure that are highly reminiscent of severe acute respiratory syndrome (SARS) caused by SARS-COV. 2017 Feb 21;8(8):12812-12819. doi: 10.18632/oncotarget.14559. 4 there is strong expression doi: 10.1038/labinvest.3700477, Sanders, J. M., Monogue, M. L., Jodlowski, T. Z., and Cutrell, J. TMPRSS2 is an endothelial cell surface protein that is involved in the viral entry and spread of coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the virus that causes COVID19. Rev. 65, 1166711675. (2010). In the current study, the frequency of TMPRSS2 rs12329760 CC than TT genotypes was significantly lower in improved patients than in dead patients. Tmprss2 Name transmembrane protease, serine 2 Synonyms D16Ertd61e, epitheliasin Feature Type protein coding gene IDs MGI:1354381 NCBI Gene: 50528 Alliance gene page Transcription Start Sites 1 TSS Location & Maps more Sequence Map Chr16:97365882-97412395 bp, - strand From Ensembl annotation of GRCm39 Genetic Map Chromosome 16, 57.53 cM, cytoband C2 (2017). However, the role of TMPRSS2 in prostatic adenocarcinoma (PRAD) remains largely unclear. TMPRSS2-/- knockout mice infected with SARS-CoV do not develop pneumonia or suffer any bodyweight loss with much lower viral replication in the lungs of these mice. The p values of all of the abovementioned cells are less than 0.001, and |rho| p < 0.05, ** General description of the gene and the encoded protein (s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project. The TMPRS22 and ERG genes are arranged tandemly on chromosome 21q22. TMPRSS2-ERG fusion gene is the most frequent, present in 40% - 80% of prostate cancers in humans. Cell 181, 271.e8280.e8. HealthScientists have known for decades that some people can be resistant to HIV infection. p < 0.01, and *** Figure 5. Angiotensin-converting enzyme 2 (ACE2) has identified as cell entry receptors for SARS-COV-2, and receptor-mediated virus entry was dependent on TMPRSS2 (Hoffmann et al., 2020; Zhou et al., 2020). Here, we interrogated the expression of all ETS family members in . Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. Nucleic Acids Res. As a prostate-specific gene, TMPRSS2 fuses with the transcription factor ERG gene in a large proportion of human prostate cancers (Nam et al., 2007) and plays an important role in selected pathological processes. HHS Vulnerability Disclosure, Help https://www.news-medical.net/health/What-is-TMPRSS2.aspx. PLoS Pathog. NewsMedical spoke to Waduda Parolari Musaid at MEDICA 2022 about Gloreha's robotics-assisted neurorehabilitation solutions. (2016). Univariate analysis was performed through GEPIA to assess the impact of TMPRSS2 on various cancer survival rates (Figure 4A). 93(6):e01815-18. We also explored the expression of TMPRSS2 between tumor and normal tissues and conducted IHC in the HPA database. 68, 927936. 181(2): 271280.e8. (B) RNA expression of TMPRSS2 in different cancers in the HAC database. Ther. (2015). We also studied the protein-protein interaction (PPI) network of TMPRSS2 in the GENEMANIA database. Cell. As a serine protease, it is involved in. PRAD: (A) sample type, (B) race, (C) age, (D) lymphatic metastatic status, and (E) TP53 mutation status (* B. When combined with urinary marker PCa antigen 3 (PCA3), urinary TMPRSS2: ERG has been reported to provide high specificity and sensitivity in diagnosing PCa [ 23 ]. Hermans KG, van Marion R, van Dekken H, Jenster G, van Weerden WM, Trapman J. TMPRSS2-203. TMPRSS2-206. The main function of the prostate is to contribute tumour microenvironment (termed . All authors contributed to the article and approved the submitted version. doi: 10.1371/journal.ppat.1004320, Lanczky, A., Nagy, A., Bottai, G., Munkacsy, G., Szabo, A., Santarpia, L., et al. JAMA 323, 18241836. Over-expression of cyclooxygenase-2 in human prostate adenocarcinoma. FOIA SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Gene expression of TMPRSS2 in the prostate is higher than in any other organ; and (C) mRNA expression level of TMPRSS2 in various cancers. Cancer Res. TMPRSS2-204. These mutations are displayed at the amino acid level across the full length of the gene by default. PMC doi: 10.1530/ERC-20-0165, Bttcher, E., Matrosovich, T., Beyerle, M., Klenk, H. -D., Garten, W., and Matrosovich, M. (2006). 2006 Nov 1;66(21):10242-6. doi: 10.1158/0008-5472.CAN-06-1986. The prostatic-related microarray GSE6956 contains gene expression profiles of primary prostate tumors resected from 69 patients and 18 non-tumor prostate tissues. The interaction between TMPRSS2 and ACE2 can promote SARS-COV-2 infection (Hoffmann et al., 2020). Differentiation 76, 576586. 2. Targets. [provided by RefSeq, Apr 2020], The Human Protein Atlas project is funded. The TMPRSS2 gene encodes a protein that belongs to the serine protease family. Transmembrane protease serine 2 (TMPRSS2) is a plasma membrane-anchored serine protease encoded by TMPRSS2 gene in humans. JAMA 315, fusion in prostate cancer. Please use one of the following formats to cite this article in your essay, paper or report: Shabir, Osman. Mucci, L. A. et al. sharing sensitive information, make sure youre on a federal The ERG gene encodes for a protein, also called ERG, that functions as a transcriptional regulator. The TMPRSS2 mRNA expression level was significantly negatively correlated with infiltrating levels of CD8+ T-cells (r = 0.345, p = 4.66e TMPRSS2 Species H. sapiens (human) Insert Size (bp) 1479 Entrez Gene TMPRSS2 ( a.k.a. GENERAL INFORMATIONi. LL and YZ wrote the manuscript. Cancer Res. The transmembrane protease serine 2:vets erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion is common in prostate cancer, while its functional role is not fully understood. Membrane-Anchored Serine Proteases in Health and Disease. Proc. The categories include: detected and not detected, where detection refers to a concentration found in the literature search. Ets family members are oncogenic transcription factors that contain a highly conserved Ets DNA binding domain and an N-terminal regulatory domain.Fusion of these gene results in androgen dependent transcription of Ets factor in prostate tumor cells. doi: 10.1093/bioinformatics/btz210, Rubin, M. A., and Chinnaiyan, A. M. J. L. I. This review focuses on the characteristics, oncogenic and rearranged mechanism, and clinical application of TMPRSS2-ETS gene fusions. Genet. We used the GEPIA database to examine the prognostic value of TMPRSS2. NX_O15393 - TMPRSS2 - Transmembrane protease serine 2 - Function. (2011). to identify novel tmprss2-erg regulated genes in pca, we performed gene profiling analyzes on rna extracted from vcap cells (a tmprss2-erg -positive, androgen-responsive pca cell line). We set Cox P/log-rank p = 0.05 as the thresholds. Unravelling the molecular and biological processes that contribute to tumor development and progressive growth, including its heterogeneity, is a challenging task. [9], TMPRSS2 protein's function in prostate carcinogenesis relies on overexpression of ETS transcription factors, such as ERG and ETV1, through gene fusion. 160, 439446. J. Cloridrato de Bromexina, um xarope de baixo custo vendido nas farmcias, www.ncbi.nlm.nih.gov/pmc/articles/PMC7502909/, https://pubmed.ncbi.nlm.nih.gov/33487145/, www.medrxiv.org//2021.03.04.21252931v1, Microbiomes in female reproductive tract linked to pregnancy following use of ART, Understanding why respiratory infections are more common in the winter, Eating ultra-processed foods increases risk of cognitive decline, Pre-existing SARS-CoV-2 antibodies may increase the breadth of mRNA vaccines, study suggests, The Psychological Strain of Chronic Physical Illness. TMPRSS2-ERG is the most frequent oncogenic gene fusion rearrangement in prostate cancer: It has been observed in almost half of prostate cancer patients and detected in about one-quarter of patients with prostatic intraepithelial neoplasia. High TMPRSS11D protein expression predicts poor overall survival in non-small cell lung cancer. (2020). Received: 24 June 2020; Accepted: 07 September 2020; Published: 30 September 2020. Isoindolinone motifs have been a central part of many pharmacological compounds, and their derivatives possess substantial anticancer . Clipboard, Search History, and several other advanced features are temporarily unavailable. (E) GSE40685 trfg vs. foxp3 ko treg precursor up. In prostate cancer ERG protooncogene frequently gains hormonal control by seizing gene regulatory elements of TMPRSS2 through genomic fusion events. In addition, we also respectively investigated the changes before and after TMPRSS2 infection with SARS-COV-2 virus in Vero E6 cells and mouse lungs. The smaller tumor focus in the peripheral zone has normal ERG arrangement (C). Samples from prostate cancer patients show an upregulation of TMPRSS2 in response to androgens. As shown in Figure 3A, prostate cancer, selected renal cell cancers, urothelial carcinoma, lung cancer, colorectal cancer, and pancreatic cancer exhibit weak to moderate membranous or granular cytoplasmic immunoreactivity. (A,B) Normal prostate (T-77100) tissue; (C,D) prostate (T-77100) tumor tissue. Subsequently, we studied the correlation among TMPRSS2, immune infiltration level, and immune cell type markers in different tumors in the TIMER database. In this study, interaction analysis was conducted on online database GEPIA3 to study the expression of PRAD based genes. . Also, TMPRSS2-/- mice showed reduced inflammatory responses compared to wild-type mice. . Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues. The prognostic value and OS rate of TMPRSS2 in PRAD were analyzed via the gene expression profiling interactive analysis (GEPIA) and UALCAN databases to explore its functional mechanism. Cancer 27, R281R292. The classification rules are the same used for the tissue specificity category. Complete information for lnc-TMPRSS2-6 gene (RNA Gene), , including: function, proteins, disorders, pathways, orthologs, and expression. Figure 7. In the normal prostate, TMPRSS2 contributes to proteolytic cascades that result in the activation of prostate-specific antigen, itself a protease involved in ejaculate production ( 9 ). The tumour growth inhibition caused by CCS1477 is sustained following drug withdrawal. 3 expression of tmprss2 is developmentally regulated and increases with ageing. 003), and it was positively correlated with macrophages (r = 0.178, p = 2.55e Cancer and COVID-19: unmasking their ties. Cell membranes anchor DPP4 along with Transmembrane Protease Serine Protease-2 (TMPRSS2) via CD-9 . 13) and CD8+ T-cells (r = 0.16, p = 1.07e Blocking TMPRSS2 could potentially be an effective clinical therapy for COVID-19. However, the prognosis of COVID-19 patients with PRAD is unclear. and TMPRSS2 are expressed in murine sustentacular cells of the olfactory epithelium which are the target of SARS-CoV-2 entry and anosmia (Bilinska et al. The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 86, 10991102. (2007). When lung function is considered, a significantly higher expression of TMPRSS2, furin and neuropilin-1 are observed in COPD with the poorest lung function (<30% FEV 1 % predicted) and, only furin . Zhongnan Hospital, Wuhan University, China, Department of Surgery, Weill Cornell Medicine, Cornell University, United States, National Institute of Malaria Research (ICMR), India. (2019). doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH743>3.0.CO;2-T, Van De Haar, J., Hoes, L. R., Coles, C. E., Seamon, K., Frohling, S., Jager, D., et al. All authors reviewed the manuscript. Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium. News-Medical. All genes with at least one isoform expected to be secreted to the extracellular environment have been annotated and classified either as secreted to blood or as locally secreted, depending on the predicted final location of the corresponding protein. Among the current hypotheses, the most plausible is that death of infected support cells in the olfactory epithelium causes, besides altered composition of the mucus, retraction of the cilia on olfactory receptor . The higher expression level suggests that TMPRSS2 possesses diverse functions in various tumors, especially in PRAD. Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s). MERS-CoV therefore uses the protease activity of TMPRSS2, among other proteases, to induce conformational changes on its spike proteins required for cell-entry . 2007 Sep;20(9):921-8. doi: 10.1038/modpathol.3800903. In this study, the expression level of TMPRSS2 in PRAD was analyzed using the oncology database. Triplicate wells of Calu-3 2B4 cells were infected with Human Coronavirus EMC 2012 (HCoV-EMC) or time-matched mock infected. [13], Cleavage of the SARS-CoV-2 S2 spike protein required for viral entry into cells can be accomplished by proteases TMPRSS2 located on the cell membrane, or by cathepsins (primarily cathepsin L) in endolysosomes. Explore the latest full-text research PDFs, articles, conference papers, preprints and more on GENE KNOCKOUT. between patient and physician/doctor and the medical advice they may provide. RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Abstract. (2020). Fold change = 1.5, value of p = 0.01, and a top 10% of gene rankings; and (D) different TMPRSS2 expressions between tumor and adjacent normal tissues. 47 In this study, we performed an extensive BLASTP search to identify ACE2 and TMPRSS2 gene homologs in lower vertebrate classes (cyclostomata, fishes, amphibians, reptiles, birds,) and each order and family in mammals. TMPRSS2 participated in the GO function analysis results of GSE30589 and GSE56677. ** This product is for in vitro and research use only. Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load. (A) GSE12484 healthy vs. peridontitis neutrophils up. PRSS10) Promoter SP6 and CMV Cloning Information Cloning method Gateway Cloning 5 sequencing primer CMV-F 3 sequencing primer EBV-Rev (Common Sequencing Primers) Resource Information Articles Citing this Plasmid 15 References Terms and Licenses At the same time, single-gene GSEA analysis of TMPRSS2 was conducted in data sets GSE30589 and GSE52920, and the GSEA of GO gene sets analysis further verified the effect of TMPRSS2 on the promoter methylation level, as shown in Figure 10. The high expression level of TMPRSS2 in the tumor and corresponding normal tissues in cancers was verified via the Oncomine database. This gene encodes a protein that belongs to the serine protease family. Virus entry can also occur through CD147, a glycoprotein present on the basolateral and apical face of cells from patients with COVID-19. In this interview, we speak with University of Warwick spin-out Cryologyx about their innovative new technology that hopes to revolutionize cell-based assays for researchers across life sciences and drug discovery. 2019 Jun 8;20(11):2802. doi: 10.3390/ijms20112802. Before TMPRSS2 Gene Functional Associations TMPRSS2 has 3,397 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 66 datasets. Onco. The results showed that the expression level of TMPRSS2 had an effect on the prognosis of PRAD. One study showed that considering the high incidence of prostate cancer and the high frequency of such gene fusion, the most common genetic abnormality described thus far in human malignancies is tmprss2-ets gene fusion (Rubin and Chinnaiyan, 2006). In this study, clinical data from TCGA3RNA-seq in UALCAN4 and clinical data from 31 cancer types were used to analyze the characteristics of tumor and normal samples in a single other clinic pathological stage, as well as the relative expression of different genes in the tumor subgroup (Chandrashekar et al., 2017). (2008). GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. * TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection. The genotype-tissue expression (GTEx) project. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. This gene is up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. Membranous expression in prostate, gastrointestinal tract, kidney and pancreas. Urology 58, 619624. Overall, these results suggested that TMPRSS2 and its associated genes were important for immune cell infiltration in the PRAD microenvironment and possibly have a more significant effect on the prognosis of PRAD. TMPRSS2-212 . The RNA data was used to cluster genes according to their expression across cell lines. Currently, . Among the possible auxiliary proteins, TMPRSS2, cysteine cathepsin B/L, glutamyl aminopeptidase, and serine protease dipeptidyl peptidase 4 (DPP4) stand out. Changes of TMPRSS after severe acute respiratory syndrome-coronavirus (SARS-COV) infection. Relat. These contain the genes encoding the spike protein, RNA replicase, 3 C-like protease, . . TMPRSS2-ERG fusions are the most predominant molecular subtype, with multiple studies showing that approximately 50% of prostate cancers from prostate-specific antigen (PSA) screened surgical cohorts are TMPRSS2-ERG fusion-positive, and greater than 90% of prostate cancers over-expressing ERG harbor TMPRSS2-ERG fusions [2,4-18]. doi: 10.1128/JVI.02232-10, Gupta, S., Srivastava, M., Ahmad, N., Bostwick, D. G., and Mukhtar, H. (2000). Because it is located on the surface of prostate cells, we found that TMPRSS2 could be a potential marker for prostate cancer diagnosis. Tu JJ, Rohan S, Kao J, Kitabayashi N, Mathew S, Chen YT. News-Medical, viewed 11 December 2022, https://www.news-medical.net/health/What-is-TMPRSS2.aspx. Table 2. Changes in TMPRSS2 expression levels caused by single nucleotide polymorphisms (SNPs) may contribute to the outcome of COVID-19. doi: 10.1038/sj.bjc.6604054, Paolonigiacobino, A., Chen, H., Peitsch, M. C., Rossier, C., and Antonarakis, S. E. J. G. (1997). Nat. This site needs JavaScript to work properly. Restrict the view to a region of the gene by dragging across the histogram to highlight the region of interest, or by using the sliders in the filters panel to the left. GSE56677 contained gene expression changes in a human airway epithelial cell line infected with two genetically distinct MERS-COV strains obtained from human patients, MERS-COV-EMC (designated EMC) and MERS-COV-London (designated LoCoV). official website and that any information you provide is encrypted Products Background Distributor Information We used tumor immune assessment resource (TIMER), Oncomine database, and GTEx project to obtain the mRNA expression level of TMPRSS2 in PRAD. Coronaviruses: an RNA proofreading machine regulates replication fidelity and diversity. The TISIDB database, known as a portal for interaction between the tumor and immune systems, integrates 988 reported immune-related anti-tumor genes, high-throughput screening techniques, molecular profiling and paracancer multinomics data, and various immunological data resources retrieved from seven public databases (Ru et al., 2019). TMPRSS2-ERG is the most common gene fusion type. Based on these data, we identified and elucidated the important role of TMPRSS2 in PRAD and the underlying mechanisms associated with its immune infiltration. Nature 579, 270273. [5][6][7] It belongs to the TMPRSS family of proteins, whose members are transmembrane proteins which have a serine protease activity. (G) GSE8515 il1 vs. il6 4 h stim mac up. (2020). (2017). The effect of thiol drugs on Vero E6-TMPRSS2 cells during the 2 h of SARS-CoV-2 infection was evaluated by the addition of 6.25 mM of each drug and 63.2 TCID 50 /mL SARS-CoV-2 simultaneously to Vero E6-TMPRSS2 cell monolayer in 96-well plates. 80, 98969898. [10], Some coronaviruses, e.g. Science 310, 644648. SARS-COV reduced the expression levels of TMPRSS in (A) GSE52920 and (B) GSE56677 lungs. Due to the high homology between SARS-COV-2 and SARS-COV, changes in TMPRSS2 expression in cells or animals infected with SARS-COV can be used as a reference for SARS-COV-2 infection (Zhou et al., 2020). 77, e108e110. TMPRSS2 is a membrane associated serine protease, expressed in the epithelium of the human respiratory tract and prostate glands. 8600 Rockville Pike J. Pathol. To explore whether TMPRSS2 exerts potential biological roles in immune infiltration, we conducted an integrated analysis based on the TIMER and TISIDB databases, analyzing the link between TMPRSS2 and immune cell infiltration as well as gene markers of immune cell subtypes in PRAD. In this work, we studied the mRNA expression level, overall survival (OS), and correlation with immune cells, among other factors. TMPRSS2: potential biomarker for COVID-19 outcomes. Unable to load your collection due to an error, Unable to load your delegates due to an error. doi: 10.1371/journal.ppat.1002315, Denison, M. R., Graham, R. L., Donaldson, E. F., Eckerle, L. D., and Baric, R. S. J. R. B. (A) Immunoreactivity of TMPRSS2 in various cancers. Gene namei. Based on the The Cancer GenomeAtlas (TCGA) database, the gene was enriched in prostate cancer in the HPA database (Figure 3B), and RNA tissue specificity was similarly enriched in prostate cancer (Figure 3C). Four such genes: the ETS-related gene (ERG), The Transmembrane Protease Serine 2 (TMPRSS2), Mouse double minute 2 homolog (MDM2), and Phosphatase and tensin homolog (PTEN) have gained recognition for their high specificity of expression in prostatic carcinomas. doi: 10.1038/ng.2653, Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., et al. It has been shown to activate hemagglutinin proteins of human influenza viruses and is implicated in prostate carcinogenesis. This study elucidated the changes of TMPRSS2 in cells and animals infected with SARS-COV and found the important role of TMPRSS2 in PRAD patients. Hence, TMPRSS2 might be activated and upregulated due to its hypomethylation, explaining the elevated TMPRSS in PRAD to a certain extent. Additionally, we performed a stratified analysis of PRAD based on patient race, age, lymphatic metastasis status, and TP53 mutation status, showing that the TMPRSS2 promoter methylation levels of older people, the lymphatic metastasis group, and the TP53 mutation group were lower than that of the control in PRAD (Figures 4BE), suggesting that PRAD TMPRSS2 promoter methylation might be activated and increase its level. This result means that patient survival is associated with gene expression and Gleason score rather than molecular signature and race (Figures 4BE). 7:e1002315. Retrieved on December 11, 2022 from https://www.news-medical.net/health/What-is-TMPRSS2.aspx. Are medical masks non-inferior to N95 respirators to prevent COVID-19 in health care workers providing routine care? UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. 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