Role Of TMPRSS2 Research Articles

SARS-CoV-2 variants as super cell fusers: cause or consequence of COVID-19 severity?

The most severe forms of coronavirus disease 2019 (COVID-19) are often associated with the presence of syncytia in the lungs resulting from cell-cell fusion mediated by the SARS-CoV-2 spike protein. In this issue, Rajah and colleagues show that the SARS-CoV-2 alpha, beta, and delta variants promote enhanced syncytia formation as compared to the original strain.

Current Trends in Prevalence and Role of Long Noncoding RNA and Gene Fusion in Prostate Cancer: An Overview

Objectives The aim of this study is to analyze the current scenario in the diagnostic modalities for prostate cancer. Materials and Methods We searched PubMed, Google Scholar, and ResearchGate for relevant data. Articles published in the last 10 years were taken into consideration. The role of long noncoding RNA and gene fusion products in the context of prostate cancer was reviewed, which included their roles in diagnosis, prognosis, and assessment of response to therapy. Results Several long noncoding RNAs (lncRNA) have been isolated and have been shown to be useful in diagnosing and prognosticating prostate cancer. We have also looked into the role of TMPRSS2:ERG gene fusion in prostate carcinoma diagnosis. These molecular parameters have been looked into due to the fact that the current parameters in use such as prostate-specific antigen have several drawbacks that limit their potential.

TMPRSS2 Correlated With Immune Infiltration Serves as a Prognostic Biomarker in Prostatic Adenocarcinoma: Implication for the COVID-2019.

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). However, the role of TMPRSS2 in prostatic adenocarcinoma (PRAD) remains largely unclear. 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. 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. 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. We also studied the protein-protein interaction (PPI) network of TMPRSS2 in the GENEMANIA 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. The function of TMPRSS2 in the dataset was further verified by gene set enrichment analysis (GSEA). In conclusion, the expression of TMPRSS2 is significantly increased in PRAD, elevated TMPRSS2 is associated with immune infiltration, and prognosis is positively correlated. 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 Role of TMPRSS2 and TMPRSS2- Inhibitors in Cell Entry Mechanism of COVID-19

The enzymes trypsin, furine and other proprotein convertases, cathepsin, transmembrane proteases (TMPRSS) and elastases play a role in the cell entry of coronaviruses (Coronaviridae). The proteases TMPRSS2 and TMPRSS11a, which are abundant in the respiratory tract and expressed on cell surfaces, promote the entry of SARS-CoV-1 viruses. For the TMPRSS protease TMPRSS11d - also known as human airway trypsin-like protease (HAT) - a proteolytic activation of the S- protein of SARS-CoV-1 was demonstrated. TMPRSS2, in turn, complexes with the ACE2 receptor, which allows efficient penetration of the virus directly at the cell surface. TMPRSS2 and TMPRSS11D activate the S protein by cleaving it into the S1 and S2 subunits, thus allowing endosome-independent cell entry at the cell membrane. Virus-based therapies include monoclonal antibodies, antiviral peptides that dock to the S protein of viruses, viral nucleic acid synthesis inhibitors and inhibitors for docking to other viral structures and accessory proteins.

Abstract 2748: The role of TMPRSS2_ERG fusions in modulating tumor microenvironment in prostate cancer

Abstract The control region of TMPRSS2 fuses with ETS transcription factor family members, particularly ERG. This occurs in ~20-50% of human prostate cancers depending on the ethnicity. TMPRSS2-ERG (T2E) fusions, however, do not display a notable phenotype in genetically engineered mouse models (GEMM) recapitulating the fusion expression and T2E also has no prognostic significance in humans, despite its high incidence. Wnt signaling has been implicated in prostate cancer. Here, we report a discovery of a role for T2E fusion that impacts the prostate stroma in pre-clinical models. The composition of stromal cells within the microenvironment in T2E mice was studied by single cell RNAseq analysis. We identified stromal cell clusters in T2E mice that differed from wild type mice in the expression of Pdgfrβ, Pdgfrα and Col1a1. Interestingly, these clusters showed an increase of expression of Wnt receptors such as Lgr5 and Fzd7 as well as Wnt ligands such as Sfrp2, Wnt2 and Wnt6. T2E GEMMs also exhibited upregulation of the Wnt-secretion regulator porcupine (PORCN-Protein-serine O-palmitoleoyltransferase) in the stroma adjacent to the T2E-expression prostate epithelial cells. Furthermore, lineage-tracing with the Wnt reporter and epithelial stem cell marker Lgr5 showed that Wnt-active cells were increased in prostatic intraepithelial neoplasia (PIN) lesions in T2E;Pten+/- mice. Strikingly, Lgr5+ cells were also found in the prostate stroma surrounding these PINs. Since, TMPRSS2/ERG fusions represent an early event in prostate tumorigenesis, here we provide a mechanism whereby induction of Wnt signaling in the stroma by T2E-expressing prostate epithelial cells increases the stem cell compartments in both epithelial and stromal cells. These data suggest that aberrant ERG-expressing prostate epithelial cells activate upregulation of Wnt signaling in stromal cells, which provides a possible route for enhancing prostate carcinogenesis. Citation Format: Hubert Pakula, Caroline F. Ribeiro, Giuseppe N. Fanelli, Rory Kirchner, Sudeepa Syamala, Basudev Chowdhury, Giorgia Zadra, Paolo Chetta, Zhe Li, Massimo Loda. The role of TMPRSS2_ERG fusions in modulating tumor microenvironment in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2748.

The role of TMPRSS2:ERG in molecular stratification of PCa and its association with tumor aggressiveness: a study in Brazilian patients.

Recurrent gene fusions between the genes TMPRSS2 and ERG have been described in prostate cancer (PCa) and are found in 27% to 79% of radical prostatectomy. This fusion transcription results in ERG overexpression, which can be detected by immunohistochemistry (IHC) and provide a potential diagnostic marker for PCa. Three tissue microarrays (TMAs) containing samples from 98 patients with PCa and one TMA of 27 samples from individuals without PCa were tested for ERG immunostaining, and the presence of TMPRSS2:ERG transcripts was confirmed by quantitative real time PCR (qRT-PCR). The results showed that 46.9% of tumors tested positive for ERG immunostaining, and this finding was consistent with the results of qRT-PCR testing (k = 0.694, p < 0.001). IHC had a specificity of 83.3% and a sensitivity of 81% in detecting TMPRSS2:ERG fusion. Patients with PSA < 4.0 ng/mL showed positive immunoreactivity for ERG (p = 0.031). Kaplan-Meier analysis suggested that ERG expression did not influence the time of biochemical recurrence. This study demonstrates that both IHC and qRT-PCR are useful tools in detecting TMPRSS2:ERG fusions. A correlation between ERG expression and clinical and pathological parameters was not found, but the frequency, specificity and recurrence of ERG in PCa suggests that it may be a potential adjunct diagnostic tool.