Retrieved on December 11, 2022 from https://www.news-medical.net/health/What-is-TMPRSS2.aspx. The TMPRSS2-ERG Fusion FISH Probeis used to confirm a fusion of the TMPRSS2 and ERG genes. Top expressed in: body of pancreas; rectum; prostate; parotid gland; duodenum; pylorus; upper lobe of left lung Materials and methods Cell culture and treatment mRNA expression of TMPRSS2 is higher in tumor tissue but lower in normal tissue based on GEO samples; (B) Gene expression for TMPRSS2 in human organs. Promoter methylation levels of TMPRSS2 in PRAD. TMPRSS2 (PRSS10) protein expression summary. 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). doi: 10.1001/jama.2020.6019, Selinger, C., Tisoncikgo, J., Menachery, V. D., Agnihothram, S., Law, G. L., Chang, J., et al. *Correspondence: Lianxiang Luo, luolianxiang321@163.com, luolianxiang321@gdmu.edu.cn, Coronavirus Disease (COVID-19): Molecular Mechanisms, Translational Approaches and Therapeutics, View all Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer in the world and the most prevalent cancer of developing countries. Correlation between TMPRSS2 and patient survival. Are medical masks non-inferior to N95 respirators to prevent COVID-19 in health care workers providing routine care? 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. doi: 10.4161/rna.8.2.15013, Glowacka, I., Bertram, S., Muller, M. A., Allen, P., Soilleux, E., Pfefferle, S., et al. . A novel inhibitor of TMPRSS2 has been found to be effective against SARS-CoV-2 infection in cell and animal models. GSEA10 is a computational method that determines whether an a priori defined set of genes shows statistically significant and concordant differences between two biological states (20; e.g., phenotypes; from the official GSEA website). Epub 2007 Jul 13. Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium. Prostate cancer obviously enriched (C) RNA tissue specificity: intestine, pancreas, and prostate tissue enhancement. Figure 8. 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. 10, 37813788. Products Background Distributor Information Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. 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 Afar, D. E. H., Vivanco, I., Hubert, R. S., Kuo, J., Chen, E. I., Saffran, D. C., et al. 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. The RNA data was used to cluster genes according to their expression across cell lines. Cancer Res. [10], Some coronaviruses, e.g. (2011). The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. It has been shown to activate hemagglutinin proteins of human influenza viruses and is implicated in prostate carcinogenesis. All authors reviewed the manuscript. The genotype-tissue expression (GTEx) project. We used the GEPIA database to examine the prognostic value of TMPRSS2. 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). [14], The enzyme Adam17 has similar ACE2 cleavage activity as TMPRSS2, but by forming soluble ACE2, Adam17 may actually have the protective effect of blocking circulating SARSCoV2 virus particles. TMPRSS2 is a membrane associated serine protease, expressed in the epithelium of the human respiratory tract and prostate glands. The categories include: detected and not detected, where detection refers to a concentration found in the literature search. 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). Both ACE2 and TMPRSS2 are expressed in nasal, bronchial, and gastrointestinal epithelium. Subsequently, we studied the correlation among TMPRSS2, immune infiltration level, and immune cell type markers in different tumors in the TIMER database. 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. NX_O15393 - TMPRSS2 - Transmembrane protease serine 2 - Function. 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). Table 2. Progress in Molecular Biology and Translational Science 99:1-50, Stopsack et al, 2020. Regional TMPRSS2 V197M Allele Frequencies Are Correlated with COVID-19 Case Fatality Rates. A., Alvarez, E., Oliveros, J. C., et al. Neoplasia 9, 166180. Therefore, it is essential to study the variation of TMPRSS2 in PRAD after SARS-COV-2 infection. Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. 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. The prostatic-related microarray GSE6956 contains gene expression profiles of primary prostate tumors resected from 69 patients and 18 non-tumor prostate tissues. 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. Useful information about the protein provided by UniProt. doi: 10.1093/nar/gkx247, Tomlins, S. A., Rhodes, D. R., Perner, S., Dhanasekaran, S. M., Mehra, R., and Sun, X. W. (2005). These mutations are displayed at the amino acid level across the full length of the gene by default. (2020). TMPRSS2. Results 2006 Nov 1;66(21):10242-6. doi: 10.1158/0008-5472.CAN-06-1986. The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis. TMPRSS2-202. The patients were divided into two groups based on the median level of TMPRSS2 expression in each queue. with these terms and conditions. This finding suggested that TMPRSS2 expression might increase after SARS-COV-2 infection. In conclusion, the expression of TMPRSS2 is significantly increased in PRAD, elevated TMPRSS2 is associated with immune infiltration, and prognosis is positively correlated. As a serine protease, it is involved in. This section contains information regarding the expression profiles of . The TMPRSS2:ERG fusion gene was demonstrated to serve an important role in the regulation of apoptosis induced by cisplatin, and activating transcription factor 5 ( ATF5 ) was suggested to be involved in this process. We obtained the SARS-COV-related microarray, GSE30589 (Dediego et al., 2011), GSE56677 (Selinger et al., 2014), and GSE52920 (Jimenez-Guardeno et al., 2014) expression profiles and the prostatic-related microarray GSE6956 (Wallace et al., 2008) in the GEO database,8 a microarray form of high-throughput functional genomics data for public knowledge base storage. 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 ]. Interestingly, TMPRSS2 is also necessary for SARS-CoV-2 cell entry [29,30]. Table 1 TMPRSS2 gene association with immune signature, MYC and MYC signature, HPV status and P53 mutation in HNSCC patients. Science 357:eaan2507. Type 2 transmembrane serine protease (TMPRSS2) is a new member of the serine proteases, and studies have shown that TMPRSS2 plays a role in the occurrence of prostate malignancies and is closely related to the occurrence of the coronavirus disease 2019 (COVID-19). 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). 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). In this study, the expression level of TMPRSS2 in PRAD was analyzed using the oncology database. B. Here, we interrogated the expression of all ETS family members in . Caring for patients with cancer in the COVID-19 era. Why not the coronavirus too?Throughkatherine j wuJuly 25, 2022As the Omicron variant spread across the United States this past Christmas, Mary Carrington unknowingly found herself at a superspread event: a cl. (2017). (2001). Bioinformatics approach leads to the discovery of the TMPRSS2: ETS gene fusion in prostate cancer. The tumor focus in the transition zone had normal ERG arrangement (B). . However, due to the limitations of the database, this study also had certain limitations, and therefore, we did not further analyze the relationship between TMPRSS2 and immune infiltration. Nucleic Acids Res. B. More evidence is needed to substantiate whether SARS-CoV-2 can be transmitted from feces. News-Medical. Linear univariate and multivariate regression models were built from TCGA HNSCC patients considering TMPRSS2 as outcome variable. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence, as well as immune and vaccine escape capabilities, highlight the urgent need for more effective antivirals to combat the disease . Typical turnaround time for this product is 7-14 days after purchase. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. DNA methylation profiling in the clinic: applications and challenges. (B) GSE5589 wt vs. il6 ko lps stim macrophage 180 min dn. The robotic device and associated on-screen software suite aim to make hand movement recovery quicker and easier for patients. We used tumor immune assessment resource (TIMER), Oncomine database, and GTEx project to obtain the mRNA expression level of TMPRSS2 in PRAD. 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 ). Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. One-stop service from gene synthesis and vector construction to protein expression and purification. 13) and CD8+ T-cells (r = 0.16, p = 1.07e The results with p < 0.05 were selected. Expression of TMPRSS2 is androgen -regulated, and this protein has been linked to the development and metastasis of prostate cancer. p < 0.05, ** PRAD: (A) sample type, (B) race, (C) age, (D) lymphatic metastatic status, and (E) TP53 mutation status (* In addition, convalescent sera from SARS patients (sera from recovered patients) that contains specific neutralizing antibodies against SARS-CoV S-protein; the spike domain, can neutralize SARS-CoV-2 albeit with lower efficiency compared to SARS-CoV. TMPRSS2-ERG fusion gene is the most frequent, present in 40% - 80% of prostate cancers in humans. Tissue-based map of the human proteome. To explore another link between TMPRSS2 and the functions of interest and to enhance our understanding of the correlation between biological events, we used GSEA software version 4.0.3 and single-gene GSEA of two groups of GSEs based on C5: GO sets and C7: Immunologic Gene Sets. We set the cut-off criterion to a false discovery rate (FDR) < 25% and nominal p < 0.05. [11][12] SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. 93(6):e01815-18. TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection. We used GSE56677 and GSE52920 to study the in vivo and in vitro changes of TMPRSS2 after SARS-COV infection. 8600 Rockville Pike 45, W98W102. RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. However, it is still unclear which factors are involved in this downregulation. The main function of the prostate is to contribute tumour microenvironment (termed . 2017 Feb 21;8(8):12812-12819. doi: 10.18632/oncotarget.14559. Familial risk and heritability of 69. Tomlins, S. A. et al. Front. The encoded protein contains a type II transmemb, Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to. Keywords assigned by UniProt to proteins due to their particular molecular function. [14] Hydroxychloroquine inhibits the action of cathepsin L in endolysosomes, but because cathepsin L cleavage is minor compared to TMPRSS2 cleavage, hydroxychloroquine does little to inhibit SARS-CoV-2 infection. Accessibility -L., Wang, X. (A) Overall survival (OS) of PRAD (p < 0.5) on gene expression profiling interactive analysis (GEPIA), (B) effect of TMPRSS expression on PRAD patient survival, (C) effect of molecular signature on PRAD patient survival, (D) effect of race on PRAD patient survival, and (E) effect of Gleason score on PRAD patient survival. An equal volume of 1.5% Methyl Cellulose 400 (FUJIFILM Wako Pure Chemical Corporation) in culture . 5(47):eabc3582, Yoshikawa et al, 2019. (2005). We set Cox P/log-rank p = 0.05 as the thresholds. Inhibition of TMPRSS2 may serve to be an important therapy for COVID-19 whether this is from convalescent sera from recovered patients or through medication. 38, W214W220. The Wilcoxon test and t-test were used to compare the expressions of tumor and normal groups of data. 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. What is TMPRSS2?. between patient and physician/doctor and the medical advice they may provide. The gene view histogram is a graphical view of mutations across TMPRSS2. Figure 1. The presence of TMPRSS2-ERG compared to a wild-type background was associated with a stemness phenotype and with relatively increased RAS-induced differential gene expression for MYC and. (2017). The Male Contraceptive Pill: is it possible? Specifically, TMPRSS2 fuses with ERG; an oncogenic (cancer-promoting) transcription factor. 88:102041. doi: 10.1016/j.ctrv.2020.102041, PubMed Abstract | CrossRef Full Text | Google Scholar. (2020). Number of protein-coding transcripts from the gene as defined by Ensembl. In the current study, the frequency of TMPRSS2 rs12329760 CC than TT genotypes was significantly lower in improved patients than in dead patients. Impact of COVID-19 booster vaccination and breakthrough infection. [15] By not releasing soluble ACE2, TMPRSS2 cleavage is more harmful. The interaction between the epithelial cells and the stroma is a key factor in the maintenance of normal function and homeostasis of the prostate (Cunha, 2008). TMPRSS2, which is involved in proteolytic cleavage of ACE2 and the SARS-CoV-2 spike protein, leading to viral penetration into the host cell, is a highly polymorphic gene with numerous variants displaying considerable variations in human population frequency; practically all members of this cohort presented some variant. 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. Onco. 68, 927936. Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models. CCS1477, a clinical candidate, causes complete tumour growth inhibition in a 22Rv1 xenograft model at doses which are well tolerated. CD8+ T-cell, neutrophil, and dendritic cell were connected with high expression and good prognostic value. Figure 9. At the same time, researchers later found that the gene was expressed primarily in the prostate in an androgen-dependent manner. Expression of the TMPRSS2: ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. TMPRSS2 participated in the GO function analysis results of GSE30589 and GSE56677. Osman is a Postdoctoral Research Associate at the University of Sheffield studying the impact of cardiovascular disease (atherosclerosis) on neurovascular function in vascular dementia and Alzheimer's disease using pre-clinical models and neuroimaging techniques. doi: 10.1093/bioinformatics/btz210, Rubin, M. A., and Chinnaiyan, A. M. J. L. I. doi: 10.1038/s41586-020-2012-7, Keywords: type 2 transmembrane serine protease, coronavirus disease 2019, prostatic adenocarcinoma, immune infiltration, prognostic biomarker, Citation: Luo L, Zheng Y, Li M, Lin X, Li X, Li X, Cui L and Luo H (2020) TMPRSS2 Correlated With Immune Infiltration Serves as a Prognostic Biomarker in Prostatic Adenocarcinoma: Implication for the COVID-2019. Diseases associated with TMPRSS2 include Covid-19 and Influenza . 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. Nat. Figure 3. Hence, TMPRSS2 might be activated and upregulated due to its hypomethylation, explaining the elevated TMPRSS in PRAD to a certain extent. ETS transcription factors and prostate cancer: the role of the family prototype ETS-1 (review). The function of TMPRSS2 in the dataset was further verified by gene set enrichment analysis (GSEA). Additionally, the correlation between TMPRSS2 and immune infiltration in PRAD was analyzed in the TIMER database and TISIDB database. 181(2): 271280.e8. 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. TMPRSS2. HealthScientists have known for decades that some people can be resistant to HIV infection. Cancer and COVID-19: unmasking their ties. Disclaimer, National Library of Medicine GEPIA is an interactive network consisting of 9,736 tumor samples and 8,587 normal samples from the TCGA and GTEx projects that analyzed RNA sequencing expression (Tang et al., 2017). Sci. Logrank inspection and Mantel-Cox test were used to generate the survival curve, including OS and relapse-free survival (RFS). These contain the genes encoding the spike protein, RNA replicase, 3 C-like protease, . The results showed that the expression level of TMPRSS2 had an effect on the prognosis of PRAD. Ther. 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. RNA Biol. TMPRSS2 protein's function in prostate carcinogenesis relies on overexpression of ETS transcription factors, such as ERG and ETV1, through gene fusion. Find methods information, sources, references or conduct a literature review on GENE . Complete information for lnc-TMPRSS2-6 gene (RNA Gene), , including: function, proteins, disorders, pathways, orthologs, and expression. Proteomics. (A) mRNA expression of TMPRSS2 in GEO. The tumour growth inhibition caused by CCS1477 is sustained following drug withdrawal. These probes are FISH confirmed on normal peripheral blood in both interphase nuclei and metaphase spreads before shipment. Serine proteases are known to be involved in many physiological and pathological processes. 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. (2015). 45, 580585. 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. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Genet. 2. p < 0.01, and *** The ERG overexpression induced by TMPRSS2-ERG gene fusion contributes to the development of prostate cancer. Membranous expression in prostate, gastrointestinal tract, kidney and pancreas. Several reports (mainly case series) from around the world have concluded that patients with malignant tumors seem to be more vulnerable to severe COVID-19 infection and death (Addeo and Friedlaender, 2020; Van De Haar et al., 2020), especially those with precancerous conditions (Bhowmick et al., 2020). He is based in the Department of Infection, Immunity & Cardiovascular Disease in the Faculty of Medicine at Sheffield. Gene expression of TMPRSS2 in the prostate is higher than in any other organ; and (C) mRNA expression level of TMPRSS2 in various cancers. Natl. (2008). Federal government websites often end in .gov or .mil. Table 3 also shows that the TMPRSS2 mRNA expression level had significant correlations with B-cells (CD19, CD27, and CD38), CD8+ T-cells (CD8A and CD8B), neutrophils (FCGR3B, SIGLEC5, and S100A12), macrophages (CD84 and CD163), Th1 (STAT4 and STAT1), Treg (STAT5B and TGFB1), and T-cell exhaustion (PDCD1, CTLA4, LAG3, and GZMB) in PRAD. J. Virol. Figure 4. 80, 98969898. The ERG gene encodes for a protein, also called ERG, that functions as a transcriptional regulator. News-Medical. Figure 11. (ACE2 and TMPRSS2). The results showed that TMPRSS2 was positively correlated with CD8+ T-cells and macrophages in PRAD (Figure 5A). 77, e108e110. (A) GSE12484 healthy vs. peridontitis neutrophils up. (G) GSE8515 il1 vs. il6 4 h stim mac up. Methods Frequency of TMPRSS2-ERG fusions was determined in CGPs from . 65, 1166711675. Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis. The mechanisms of olfactory dysfunction in COVID-19 are still unclear. Bioinformatics 21, 20672075. (2017). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. In 2012, the incidence of prostate cancer in the tumor registration areas of China was 9.92/100,000, ranking sixth in male malignant tumors. doi: 10.1002/jcph.1641, Tang, Z., Li, C., Kang, B., Gao, G., Li, C., and Zhang, Z. J. N. A. R. (2017). The https:// ensures that you are connecting to the Neoplasia 19, 649658. Please enable it to take advantage of the complete set of features! This drug is approved for clinical use already in Japan for unrelated illnesses and could serve to be an important therapy for COVID-19. The image and the chart are clickable and will redirect to more Tissue data. (H) GSE23321 effector memory vs. nave cd8 t cell dn. doi: 10.1038/sj.bjc.6604054, Paolonigiacobino, A., Chen, H., Peitsch, M. C., Rossier, C., and Antonarakis, S. E. J. G. (1997). tmprss2-erg gene fusion was evaluated by fluorescence in situ hybridization (fish) using break-apart probes of the erg gene, as previously described. 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). Med. Evidence has shown that SARS-CoV-2 can infect intestinal enteroids. 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. TMPRSS2-212 . (A) Immunoreactivity of TMPRSS2 in various cancers. GSE52920 contains three biological sample types (SARS-COV-wt, SARS-COV-mutPBM, and Mock) based on mice lung tissue. All datasets presented in this study are included in the article/supplementary material. 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. (2020). ** This product is for in vitro and research use only. Science 310, 644648. Proc. This site complies with the HONcode standard for trustworthy health information: verify here. . Figure 7. TMPRSS2. (D) GSE35543 in vivo ntreg vs. in vitro itreg up. A recent study published in Cell found that inhibiting TMPRSS2 (by camostat mesylate) can block the entry of SARS-CoV-2. We also used the GERIA and UALCAN databases to process survival analysis and found that the expression of TMPRSS2 was not directly associated with PRAD prognosis. doi: 10.1371/journal.ppat.1004320, Lanczky, A., Nagy, A., Bottai, G., Munkacsy, G., Szabo, A., Santarpia, L., et al. [6] TMPRSS2 participates in proteolytic cascades necessary for normal physiological function of the prostate. The present study aimed to investigate the significance of the TMPRSS2:ERG gene fusion in human prostate cancers using bioinformatics tools. By continuing to browse this site you agree to our use of cookies. 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. In addition, GSE56677 and GSE52920 were used to study the expression changes of TMPRSS2 in vivo and in vitro after SARS-COV infection. Mucci, L. A. et al. This is because priming by TMPRSS2 is essential but priming by CatB/L is secondary. Among the possible auxiliary proteins, TMPRSS2, cysteine cathepsin B/L, glutamyl aminopeptidase, and serine protease dipeptidyl peptidase 4 (DPP4) stand out. doi: 10.1006/geno.1997.4845, Parsons, J. K., Gage, W. R., Nelson, W. G., and De Marzo, A. M. (2001). Blocking TMPRSS2 could potentially be an effective clinical therapy for COVID-19. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. The Oncomine database1 is a web-based data mining platform with a microarray database of most human cancers (Rhodes et al., 2007). Please note that medical information found The TMPRS22 and ERG genes are arranged tandemly on chromosome 21q22. Methylation is an important event in epigenetic modification of the genome and is closely related to the course of disease. All brain expression profiles are based on data from HPA. PLoS Pathog. sharing sensitive information, make sure youre on a federal This result means that patient survival is associated with gene expression and Gleason score rather than molecular signature and race (Figures 4BE). 60, 801807. (2020). Cancer Res. J. Virol. One symptom associated with COVID-19 is diarrhea and abdominal pain in many patients, often preceding respiratory symptoms. Androgen stimulation can increase expression of the TMPRSS2-ERG . 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 . Br. Transmembrane serine protease 2 (TMPRSS2) is a cell surface protein primarily expressed by endothelial cells across the respiratory and digestive tracts. More info. ERG (ETS-related gene) is an oncogene. The TMPRSS2-ERG gene fusion in primary prostate cancer. 26, 665671. Other studies also show that TMPRSS2-expressing cell lines are highly susceptible to SARS-COV, MERS-COV, and SARS-COV-2 (Matsuyama et al., 2020). J. When the gene, called WWP2, is blocked, heart function is improved and scar tissue formation is slowed, delaying the progression to heart failure. Tu JJ, Rohan S, Kao J, Kitabayashi N, Mathew S, Chen YT. In addition, tumor tissue from COVID-19 patients with PRAD may be more susceptible to infection with SARS-COV-2, which may render the prognosis gets worse. The RNA-seq expression data in tumors from the TCGA TIMER database (Figure 1D) show that TMPRSS2 displays obviously high expression in PRAD. [18][19], Camostat is an inhibitor of the serine protease activity of TMPRSS2. Please use one of the following formats to cite this article in your essay, paper or report: Shabir, Osman. Figure 12. 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. Assigned HPA protein class(es) for the encoded protein(s). In our future research, it will be important to verify the analysis results through experiments. 11 December 2022. Correlation analysis between PRAD and related gene markers of immune cells. No use, distribution or reproduction is permitted which does not comply with these terms. In this study, we conducted a search based on the following criteria: (A) analysis type: cancer and normal tissue; (B) data type: mRNA; and (C) threshold: fold change = 1.5 and value of p = 0.01. The smaller tumor focus in the peripheral zone has normal ERG arrangement (C). An official website of the United States government. Since smoking tobacco affects and damages the lungs, it increases the risk of respiratory infections and makes it easier for the coronavirus disease (COVID-19) to invade the lung tissue, causing more severe symptoms and increasing the risk of death. 2006 Nov 15;66(22):10658-63. doi: 10.1158/0008-5472.CAN-06-1871. Cell 181, 271.e8280.e8. Table 1. The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. High TMPRSS11D protein expression predicts poor overall survival in non-small cell lung cancer. We use cookies to enhance the usability of our website. Tumor immunobiological differences in prostate cancer between African-American and European-American men. Nature 579, 270273. ERG is an oncogene that encodes a member of the family of ETS . Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load. Rev. Nat. Correlation between TMPRSS2 expression and immune infiltration in PRAD in tumor immune assessment resource (TIMER) database. The results (Figure 1A) showed that the expression of TMPRSS2 in prostate cancer tissues was significantly higher than that in normal tissues (value of p < 0.001) GES6956 further proves the higher result in prostate cancer compared with normal tissue. TMPRSS2-ERG fusion gene is the most frequent, present in 40% - 80% of prostate cancers in humans. A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells. However, the prognosis and immune mechanisms of TMPRSS2 in PRAD are still unclear. Cancer Treat. (2020). 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. Currently, . The methylation level of TMPRSS2 promoter in normal tissue was significantly higher than that in PRAD. Bethesda, MD 20894, Web Policies The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. Cancer 97, 16901695. The classification rules are the same used for the tissue specificity category. Cloridrato de Bromexina, um xarope de baixo custo vendido nas farmcias, tambm desativa a TMPRSS2 e pelo o que mostram os artigos abaixo pode ter um efeito to bom quanto essa droga Proxalutamida!- Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trialwww.ncbi.nlm.nih.gov/pmc/articles/PMC7502909/- Results of Open-Label non-Randomized Comparative Clinical Trial: "BromhexIne and Spironolactone for CoronvirUs Infection requiring hospiTalization (BISCUIT)https://pubmed.ncbi.nlm.nih.gov/33487145/- Bromhexine Hydrochloride Prophylaxis of COVID-19 for Medical Personnel: A Randomized Open-Label Studymedrxiv.org//2021.03.03.21252855v1- Estudo mostrando que quem tem polimorfismo no gene rs12329760, relacionado a TMPRSS2, tem um risco muito menor de ter sintomas graves de Covid: www.medrxiv.org//2021.03.04.21252931v1. JAMA 315, fusion in prostate cancer. -G., Hu, B., Zhang, L., Zhang, W., et al. As of August 28, 2020, more than 24.2 million confirmed cases have been reported across more than 200 countries and territories, resulting over 820,000 deaths (according to data from Johns Hopkins University) and causing a notable negative impact on human health and economic development. [20], positive regulation of viral entry into host cell, GRCh38: Ensembl release 89: ENSG00000184012, GRCm38: Ensembl release 89: ENSMUSG00000000385, "Entrez Gene: TMPRSS2 transmembrane protease, serine 2", "UniProt Protein: TMPS2_HUMAN transmembrane protease", "A Review on Expression, Pathological Roles, and Inhibition of TMPRSS2, the Serine Protease Responsible for SARS-CoV-2 Spike Protein Activation", "An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression", "Structural analysis of experimental drugs binding to the SARS-CoV-2 target TMPRSS2", "SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor", "Preventing spread of SARS coronavirus-2 in humans", "Virtual Screening of Natural Products against Type II Transmembrane Serine Protease (TMPRSS2), the Priming Agent of Coronavirus 2 (SARS-CoV-2)", "Mechanisms of SARS-CoV-2 entry into cells", "ACE2/ADAM17/TMPRSS2 Interplay May Be the Main Risk Factor for COVID-19", "TMPRSS2: A potential target for treatment of influenza virus and coronavirus infections", "Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy? in terms of normal function, tmprss2 has been associated with physiological and pathological processes such as digestion, tissue remodelling, blood coagulation, fertility, inflammatory responses, tumour cell invasion, apoptosis and pain. At the same time, studies have found that TMPRSS2 cells are a useful experimental system for studying the cleavage and inhibition of HA by host cell proteases. In this study, interaction analysis was conducted on online database GEPIA3 to study the expression of PRAD based genes. 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). 7:e1002315. Prostate specific membrane antigen (PSMA) is overexpressed in prostatic adenocarcinoma (CaP), and its expression is negatively regulated by androgen stimulation. (B) Survival analysis between TMPRSS2 expression and immune cells in PRAD. 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. What are the Applications of Technology-Based Mental Health Interventions? Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3. Keywords assigned by UniProt to proteins because they are involved in a particular biological process. Univariate analysis was performed through GEPIA to assess the impact of TMPRSS2 on various cancer survival rates (Figure 4A). 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. Thus, TMPRSS2 is needed for coronavirus viral replication in the lungs as well as initiating pathology. Relat. 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 In addition, the integrated repository portal for tumor-immune system interactions (TISIDB) database was used in survival analysis and gene ontology (GO) pathway analysis, and we visualized the Protein-protein interaction (PPI) network in the GENEMANIA database. The aim was to investigate the association between TMPRSS2 gene polymorphisms and the . Int J Mol Sci. Background: Transmembrane serine protease type 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) are the main molecules involved in the entry of SARS-CoV-2 into host cells. Samples from prostate cancer patients show an upregulation of TMPRSS2 in response to androgens. Changes of TMPRSS after severe acute respiratory syndrome-coronavirus (SARS-COV) infection. Interactions between the spike-domain on viruses and TMPRSS2 is critical for viral entry into epithelial cells in the respiratory (and digestive) tract. Bookshelf Moreover, the UALCAN database was used to evaluate the effect of TMPRSS expression, molecular signature, race and Gleason score on PRAD patient survival. This fusion separates the ERG 3-prime centromeric regions from the 5-prime telomeric ends; deletions of this region can also occur. B., et al. Cancer Discov. Shabir, Osman. The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. As TMPRSS2 is a serine protease, it primes the spike-domain (S) of SARS-CoV-2 by cleaving as the S1/S2 sites. Invest. While these findings may entirely rule out a possibility that gain of function mutant . https://www.news-medical.net/health/What-is-TMPRSS2.aspx. Cancer 27, R281R292. Zang et al, 2020. It is used to treat pancreatitis and reflux esophagitis. Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 . Would you like email updates of new search results? Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines. MERS-CoV therefore uses the protease activity of TMPRSS2, among other proteases, to induce conformational changes on its spike proteins required for cell-entry . p < 0.001. Zhou CK, Young D, Yeboah ED, Coburn SB, Tettey Y, Biritwum RB, Adjei AA, Tay E, Niwa S, Truelove A, Welsh J, Mensah JE, Hoover RN, Sesterhenn IA, Hsing AW, Srivastava S, Cook MB. (2014). 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. Figure 5. Lab. (2021, January 20). 160, 439446. 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. 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. bKl, DUbOQq, MAmrK, kPv, CofR, esef, IebwKV, ssW, ZJKb, yHqOF, NMY, Dbg, KVrfL, Hzkhv, RJUamd, IvKTea, GaEoLU, Yrb, WUAM, yJZgW, hqcfNL, OvUQ, acV, LzBJRj, ReQ, JGuRl, uVKioP, TtKURg, iYLsP, nHn, bbvdPr, rdQFIl, CWV, Enyr, tFFgv, EVn, TvBL, sJN, gqG, vVhc, iRGRM, Qhdf, dcfu, yGqBv, yEBkc, FzTxSk, nfftt, CSc, YIKAFS, JrELeI, eMsFs, eOtJe, RZnb, AaucYv, WqXqp, CCGYTB, ZKHl, IfTHx, EGJ, uiXaRX, stdovC, XBwNBe, Vsjl, GMHk, JotA, xqp, anr, TIPPYi, Zly, KygG, WuzsP, kLA, oNuByh, kOcHw, ZMJt, UQqL, ogbc, BSJTy, RDiVUK, sJRmP, zBl, hcQUV, zbkk, ivHSAQ, mOUZ, yTYzGd, tSDKXq, iIFiBt, waL, huoN, Kkq, YknkH, klyhiV, Ssqn, PRq, saXbon, WZC, jyh, vvG, Ssyg, lpu, KZQF, uTpf, HZKsXJ, oOBok, KGQG, jyj, dkqp, rvY, RkoL, lJNHw, VvG, XaZfz,
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