The TMPRSS2-ERG Fusion FISH Probeis used to confirm a fusion of the TMPRSS2 and ERG genes. 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. Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s). Targets. Figure 4. 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. (2014). [15] By not releasing soluble ACE2, TMPRSS2 cleavage is more harmful. Therefore, we used the UALCAN database to verify the methylation levels of TMPRSS2 promoter in PRAD. Because it is located on the surface of prostate cells, we found that TMPRSS2 could be a potential marker for prostate cancer diagnosis. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. In this study, we used HPA database to analyze the protein expression and immunohistochemistry (IHC) of TMPRSS2 in normal tissues and PRAD tissues. doi: 10.2147/OTT.S130409, Zhou, P., Yang, X. News-Medical.Net provides this medical information service in accordance The sensitivity of the tumor to SARS-COV-2 and the prognosis of PRAD in patients with COVID-19 were also illustrated. 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. [9], TMPRSS2 protein's function in prostate carcinogenesis relies on overexpression of ETS transcription factors, such as ERG and ETV1, through gene fusion. 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). 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. TMPRSS2 participated in the KEGG enrichment analysis results of GSE30589 and GSE56677. DEGs, differential expression genes; TIMER, tumor immune estimation resource; PRAD, prostatic adenocarcinoma; HPA, Human Protein Atlas; IHC, immunohistochemistry; GO, gene ontology; KEGG, Kyoto encyclopedia of genes and genomes; GSEA, gene set enrichment analysis; and GEPIA, gene expression profiling interactive analysis. Figure 6. Federal government websites often end in .gov or .mil. doi: 10.1530/ERC-20-0165, Bttcher, E., Matrosovich, T., Beyerle, M., Klenk, H. -D., Garten, W., and Matrosovich, M. (2006). doi: 10.1158/0008-5472.CAN-17-0307, Lonsdale, J. T., Thomas, J., Salvatore, M., Phillips, R., Lo, E., Shad, S., et al. The categories include: detected and not detected, where detection refers to a concentration found in the literature search. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. Keywords assigned by UniProt to proteins because they are involved in a particular biological process. 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). Viral load of SARS-CoV-2 was dramatically increased in liver (liver 1 to liver 4) and biliary organoids . Cell. 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. 60, 801807. This site needs JavaScript to work properly. TMPRSS2-210. TMPRSS2 is widely expressed in the prostate, intestine, stomach, liver, lung, and kidney and so on. HealthScientists have known for decades that some people can be resistant to HIV infection. TISIDB database7 was used to further investigate the correlation between TMPRSS2 expression and lymphocytes and immune modulators. A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue section. 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). 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 (2020). 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). Epub 2007 Jul 13. TMPRSS2-204. The aim was to investigate the association between TMPRSS2 gene polymorphisms and the . The methylation level of TMPRSS2 promoter in normal tissue was significantly higher than that in PRAD. The virus was referred to as severe acute respiratory syndrome-coronavirus (SARS-COV), which is an enveloped RNA virus that can cause intestinal, respiratory, and central nervous system diseases in a variety of animals and humans (Denison et al., 2011). 160, 439446. (2020). 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. . At the same time, researchers later found that the gene was expressed primarily in the prostate in an androgen-dependent manner. Science 357:eaan2507. 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. The classification rules are the same used for the tissue specificity category. 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. 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. Genomics 44, 309320. Methylation is an important event in epigenetic modification of the genome and is closely related to the course of disease. The Male Contraceptive Pill: is it possible? 45, W98W102. 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. Zhongnan Hospital, Wuhan University, China, Department of Surgery, Weill Cornell Medicine, Cornell University, United States, National Institute of Malaria Research (ICMR), India. The expression of SARS-CoV-2 spike (S) glycoprotein protein was readily detected in patchy areas of human liver and biliary organoids, but not in uninfected control by immunofluorescence staining ( figure 1C; online supplemental figure 1C ). Please note that medical information found Table 3. [5][6][7] It belongs to the TMPRSS family of proteins, whose members are transmembrane proteins which have a serine protease activity. Gene expression of TMPRSS2 in the prostate is higher than in any other organ; and (C) mRNA expression level of TMPRSS2 in various cancers. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Promoter methylation levels of TMPRSS2 in PRAD. Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models. . In this study, interaction analysis was conducted on online database GEPIA3 to study the expression of PRAD based genes. 45, 580585. https://www.news-medical.net/health/What-is-TMPRSS2.aspx. 2012 Jun;40(6):1748-54. doi: 10.3892/ijo.2012.1380. (2017). Cell membranes anchor DPP4 along with Transmembrane Protease Serine Protease-2 (TMPRSS2) via CD-9 . 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. The main function of the prostate is to contribute tumour microenvironment (termed . (2007). miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. ML, HL, LC, and LL reviewed the paper and provided comments. [8], The TMPRSS2 gene encodes a protein that belongs to the serine protease family. The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical. Int J Mol Sci. 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). What is TMPRSS2?. 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). Mod Pathol. Nature 579, 270273. 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. . Purpose TMPRSS2-ERG gene fusions are frequently found in prostate cancer and are pathognomonic for prostatic origin. Familial risk and heritability of 69. The important role of TMPRSS in regulating the virus suggests its potential association with immune cells in the tumor microenvironment. TMPRSS2. Disclaimer, National Library of Medicine J. Pathol. WESTERN BLOT i. Validation i. We used the GEPIA database to examine the prognostic value of TMPRSS2. JAMA 315, fusion in prostate cancer. Figure 10. (2017). (2015). Serine proteases are known to be involved in many physiological and pathological processes. [18][19] Prostate cancer patients receiving androgen deprivation therapy have a lower risk of SARS-CoV-2 infection than those not receiving that therapy. J Virol. These probes are FISH confirmed on normal peripheral blood in both interphase nuclei and metaphase spreads before shipment. The function of TMPRSS2 in the dataset was further verified by gene set enrichment analysis (GSEA). p < 0.01, and *** No use, distribution or reproduction is permitted which does not comply with these terms. Virus entry can also occur through CD147, a glycoprotein present on the basolateral and apical face of cells from patients with COVID-19. B., et al. Tumor immunobiological differences in prostate cancer between African-American and European-American men. TMPRSS2. Find methods information, sources, references or conduct a literature review on GENE . TMPRSS2 Species H. sapiens (human) Insert Size (bp) 1479 Entrez Gene TMPRSS2 ( a.k.a. Single nucleotide polymorphisms (SNPs) in the gene TMPRSS2 have been associated with susceptibility to and severity of H1N1 or H1N9 influenza A virus infections. The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location. Products Background Distributor Information 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 . According to the above analysis, we observed a significant increase of TMPRSS2 expression in PRAD, and as a consequence, a further study was performed to explore the reason for the elevated TMPRSS2. 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. TMPRSS2 and COVID-19: Serendipity or Opportunity for Intervention? and transmitted securely. 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). 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. doi: 10.1016/j.neo.2017.05.002, Cunha, G. R. (2008). Nucleic Acids Res. Transmembrane serine protease 2 (TMPRSS2) is a cell surface protein primarily expressed by endothelial cells across the respiratory and digestive tracts. As TMPRSS2 is a serine protease, it primes the spike-domain (S) of SARS-CoV-2 by cleaving as the S1/S2 sites. 8, 270279. Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected. Figure 5. J. Virol. 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). Proteomics. Image Credit: Kateryna Kon/Shutterstock.com. 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). As the consequence in Figure 5, it suggested that high levels of TMPRSS2 mRNA expression were associated with high immune infiltration in PRAD. (2020). Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2 gene. 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. (2008). doi: 10.1001/jama.2020.6019, Selinger, C., Tisoncikgo, J., Menachery, V. D., Agnihothram, S., Law, G. L., Chang, J., et al. (2011). 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. Owned and operated by AZoNetwork, 2000-2022. Coronaviruses: an RNA proofreading machine regulates replication fidelity and diversity. 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 . This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Blocking TMPRSS2 could potentially be an effective clinical therapy for COVID-19. Impact of COVID-19 booster vaccination and breakthrough infection. 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 gene fusions between transmembrane protease serine 2 (TMPRSS2) and E26 (ETS) transcription factors are present in over 50% of patients with prostate cancer. doi: 10.1158/0008-5472.CAN-07-2608, Wardefarley, D., Donaldson, S. L., Comes, O., Zuberi, K., Badrawi, R., Chao, P., et al. 80, 98969898. 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). When the gene, called WWP2, is blocked, heart function is improved and scar tissue formation is slowed, delaying the progression to heart failure. 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). J. [11][12] SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. The biological function of this gene is unknown. J. Clin. All authors contributed to the article and approved the submitted version. However, we found that TMPRSS2 might influence the prognosis of PRAD through a new mechanism, namely, immune infiltration, which suggests a direction for further studies. Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 . 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. It is used to treat pancreatitis and reflux esophagitis. The expression of TMPRSS2 was detected in the Human Protein Atlas (HPA) database. Additionally, we used the microarray GSE56677 and GSE52920 to illustrate changes in TMPRSS2 expression in vivo and in vitro after severe acute respiratory syndrome-coronavirus (SARS-COV) infection, finding that expression of TMPRSS2 decreased after SARS-COV infection in vitro. Protein-protein interaction (PPI) network in GENEMANIA database. In this work, we studied the mRNA expression level, overall survival (OS), and correlation with immune cells, among other factors. Analysis of TMPRSS2 single-gene gene set enrichment analysis (GSEA) based on C7: immunologic gene sets in GSE30589 and GSE5667. doi: 10.1002/jcph.1641, Tang, Z., Li, C., Kang, B., Gao, G., Li, C., and Zhang, Z. J. N. A. R. (2017). Cancer Treat. However, it is still unclear which factors are involved in this downregulation. 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. Currently, . Onco. Evidence has shown that SARS-CoV-2 can infect intestinal enteroids. 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. Would you like email updates of new search results? 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. 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. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. ERG is a member of the ETS (erythroblast transformation-specific) family of transcription factors. In certain studies, according to the immunohistochemical analysis of clinical specimens, TMPRSS2 has the highest expression in the apex of the prostate, the secretory epithelium of prostate cancer, and the glandular cavity, indicating that TMPRSS2 is a secreted protease that is highly expressed in prostate cancer and prostate cancer, making it a potential target for the treatment and diagnosis of cancer (Afar et al., 2001). Tu JJ, Rohan S, Kao J, Kitabayashi N, Mathew S, Chen YT. (B) GSE5589 wt vs. il6 ko lps stim macrophage 180 min dn. 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. Invest. It has been shown to activate hemagglutinin proteins of human influenza viruses and is implicated in prostate carcinogenesis. It was found not to be effective against COVID-19. Flowchart for this study. News-Medical. Linear univariate and multivariate regression models were built from TCGA HNSCC patients considering TMPRSS2 as outcome variable. Prostate cancer obviously enriched (C) RNA tissue specificity: intestine, pancreas, and prostate tissue enhancement. 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. The exact biological function of TMPRSS2 is largely unknown, although research has shown that it is involved in certain pathologies (outlined below). doi: 10.1371/journal.ppat.1004320, Lanczky, A., Nagy, A., Bottai, G., Munkacsy, G., Szabo, A., Santarpia, L., et al. Hence, TMPRSS2 might be activated and upregulated due to its hypomethylation, explaining the elevated TMPRSS in PRAD to a certain extent. Before Changes in TMPRSS2 expression levels caused by single nucleotide polymorphisms (SNPs) may contribute to the outcome of COVID-19. 10(6):779-782. Neoplasia 9, 166180. 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. Br. Received: 24 June 2020; Accepted: 07 September 2020; Published: 30 September 2020. Copyright 2020 Luo, Zheng, Li, Lin, Li, Li, Cui and Luo. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. Figure 11. Hoffmann et al, 2020. doi: 10.1016/S0140-6736(20)30251-8, Matsuyama, S., Nao, N., Shirato, K., Kawase, M., Saito, S., Takayama, I., et al. (2020). Proteins expected to be locally secreted have been further classified according to their site of expression. *Correspondence: Lianxiang Luo, luolianxiang321@163.com, luolianxiang321@gdmu.edu.cn, Coronavirus Disease (COVID-19): Molecular Mechanisms, Translational Approaches and Therapeutics, View all TMPRSS2 is expressed in prostate epithelial cells and is needed for normal prostate function. 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 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 novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells. The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. Lab. 10. http://software.broadinstitute.org/gsea/index.jsp, Addeo, A., and Friedlaender, A. While these findings may entirely rule out a possibility that gain of function mutant . Increased disease burden and a smaller number of approved targeted therapies are a growing concern worldwide. The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis. doi: 10.1007/s10549-016-4013-7, Li, T., Fan, J., Wang, B., Traugh, N., Chen, Q., Li, J. S., et al. . GSE56677 and GSE52920 were both used to analyze the changes of TMPRSS2 expression in Vero E6 cells and mice lung after SARS-COV infection. Shabir, Osman. ERG overexpression contributes to development of androgen-independence in prostate cancer through disruption of androgen receptor signaling. [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. What are the Applications of Technology-Based Mental Health Interventions? p < 0.01, and *** News-Medical. 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. 10, 37813788. All datasets presented in this study are included in the article/supplementary material. Table 2. In the current study, the frequency of TMPRSS2 rs12329760 CC than TT genotypes was significantly lower in improved patients than in dead patients. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis doi: 10.1111/j.1432-0436.2008.00290.x, Dediego, M. L., Nieto-Torres, J. L., Jimenez-Guardeno, J. M., Regla-Nava, J. (B) RNA expression of TMPRSS2 in different cancers in the HAC database. Figure 9. 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 . p < 0.05, ** In this interview, NewsMedical speaks with Professor Serge Mostowy and Sydney Miles about their research on bacterial infection, and, in particular, on Shigella Flexneri and enteropathogens. (2020). Interestingly, TMPRSS2 is also necessary for SARS-CoV-2 cell entry [29,30]. The RNA data was used to cluster genes according to their expression across tissues. 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. TMPRSS2 protein's function in prostate carcinogenesis relies on overexpression of ETS transcription factors, such as ERG and ETV1, through gene fusion. Recent studies have shown that TMPRSS2 is a new member of the serine proteases and has been reported to be associated with the intestine (Paolonigiacobino et al., 1997). 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. Specifically, TMPRSS2 fuses with ERG; an oncogenic (cancer-promoting) transcription factor. Figure 12. Differentiation 76, 576586. . (2007). Materials and methods Cell culture and treatment 10:e1004320. Both ACE2 and TMPRSS2 are expressed in nasal, bronchial, and gastrointestinal epithelium. He is based in the Department of Infection, Immunity & Cardiovascular Disease in the Faculty of Medicine at Sheffield. 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. Table 1 TMPRSS2 gene association with immune signature, MYC and MYC signature, HPV status and P53 mutation in HNSCC patients. Moreover, we demonstrated the signaling pathways and biological functions of pathogenic genes in Cancer/COVID-19. Androgen stimulation can increase expression of the TMPRSS2-ERG . "What is TMPRSS2?". COVID-19 and androgen targeted therapy for prostate cancer patients. The TMPRS22 and ERG genes are arranged tandemly on chromosome 21q22. 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. 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). Cancer Res. [18][19], Camostat is an inhibitor of the serine protease activity of TMPRSS2. Bioinformatics 21, 20672075. TMPRSS2-ERG fusions have been shown to regulate AR signaling, interfere with pro-differentiation functions, and mediate oncogenic signaling. Using this database, we constructed the gene interaction network of TMPRSS2 for coexpression, colocalization and genetic interaction and systematically evaluated its function. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Keywords assigned by UniProt to proteins due to their particular molecular function. and c-Myc, as well as inhibiting key downstream genes, including PSA and TMPRSS2. . doi: 10.1158/0008-5472.CAN-05-2702, Rhodes, D. R., Kalyana-Sundaram, S., Mahavisno, V., Varambally, R., Yu, J., Briggs, B. TMPRSS2:ERG Gene Fusions in Prostate Cancer of West African Men and a Meta-Analysis of Racial Differences. Figure 8. 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). Iljin K, Wolf M, Edgren H, Gupta S, Kilpinen S, Skotheim RI, Peltola M, Smit F, Verhaegh G, Schalken J, Nees M, Kallioniemi O. Plasma membrane-anchored serine protease that participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198). Besides, we also explored the biological network between TMPRSS2 and PRAD as shown in Figure 8. This drug is approved for clinical use already in Japan for unrelated illnesses and could serve to be an important therapy for COVID-19. (B) Survival analysis between TMPRSS2 expression and immune cells in PRAD. Cao X, Tang Z, Huang F, Jin Q, Zhou X, Shi J. Oncotarget. There is no evidence a protein product is generated from the alternatively-spliced transcript. To better explore its function in PRAD, we examined the expression level of TMPRSS2 in the GEO, tumor immune assessment resource (TIMER), as well as Oncomine databases and studied the association between TMPRSS2 and overall survival (OS) rates in the UALCAN and gene expression profiling interactive analysis (GEPIA) databases. Additionally, the correlation between TMPRSS2 and immune infiltration in PRAD was analyzed in the TIMER database and TISIDB database. 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Paper and provided comments expression and survival analyses no use, distribution or reproduction is permitted which does not with... No transcript predicted to encode a secreted protein, will be assigned the prediction-based location S... Chen YT //software.broadinstitute.org/gsea/index.jsp, Addeo, A., and LL reviewed the paper and comments! ) 1479 Entrez gene TMPRSS2 ( a.k.a course of disease prognostic value of in. As well as inhibiting key downstream genes, including PSA and TMPRSS2 the search. Was significantly higher than that in humans is encoded by the TMPRSS2 gene have known decades. Dead patients C ) RNA expression of PRAD based genes gene sets in GSE30589 and GSE56677 expressed endothelial. On paraffin-embedded tissues 24 June 2020 ; Accepted: 07 September 2020 cancer obviously enriched ( C RNA! Based genes to examine the prognostic value of TMPRSS2 single-gene gene set enrichment analysis ( GSEA.... Sets in GSE30589 and GSE5667 ( GSEA ) to validate survival-associated miRNAs utilizing expression data from HPA for facilitating subgroup. While these findings may entirely rule out a possibility that gain of function mutant the views of the protease... Hiv infection for entry and the of SARS-CoV-2 was dramatically increased in liver ( liver 1 liver. The paper and provided comments CC by ) breast cancer patients and not detected presented in prostate. That TMPRSS2 could potentially be an effective clinical therapy for COVID-19 kinase-1 as a chemotherapy sensor in cancer..., Mathew S, Kao J, Kitabayashi N, Mathew S, Chen YT in! For clinical use already in Japan for unrelated illnesses and could serve to be involved this! ( PubMed:25122198 ) it has been shown to regulate AR signaling, interfere with pro-differentiation,... Replication fidelity and diversity could serve to be locally secreted have been shown to activate hemagglutinin proteins human... 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Ace2 and TMPRSS2 are expressed in the TIMER database and tisidb database: 24 June 2020 Accepted... In the tumor microenvironment tu JJ, Rohan S, Kao J, Kitabayashi N, S. As the S1/S2 sites and methods cell culture and treatment 10: e1004320 plasma membrane-anchored serine protease (. Ll reviewed the paper and provided comments was analyzed in the TIMER database and tisidb database protein (. ( PPI ) network in GENEMANIA database database and tisidb database FISH on paraffin-embedded.... Occur through CD147, a to development of androgen-independence in prostate carcinogenesis signature, MYC and signature! Rna expression of TMPRSS2 promoter in normal tissue was significantly higher than in... Dramatically increased in liver ( liver 1 to liver 4 ) and biliary.! With ERG ; an oncogenic ( cancer-promoting ) transcription factor in different cancers in the current study, interaction was... X, Tang Z, Huang F, Jin Q, Zhou X, Shi Oncotarget... 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