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1.
J Cell Mol Med ; 25(8): 4157-4165, 2021 04.
Article in English | MEDLINE | ID: covidwho-1091045

ABSTRACT

TMPRSS2 (OMIM: 602060) is a cellular protease involved in many physiological and pathological processes, and it facilitates entry of viruses such as SARS-CoV-2 into host cells. It is important to predict the prostate's susceptibility to SARS-CoV-2 infection in cancer patients and the disease outcome by assessing TMPRSS2 expression in cancer tissues. In this study, we conducted the expression profiles of the TMPRSS2 gene for COVID-19 in different normal tissues and PRAD (prostate adenocarcinoma) tumour tissues. TMPRSS2 is highly expressed in normal tissues including the small intestine, prostate, pancreas, salivary gland, colon, stomach, seminal vesicle and lung, and is increased in PRAD tissues, indicating that SARS-CoV-2 might attack not only the lungs and other normal organs, but also in PRAD cancer tissues. Hypomethylation of TMPRSS2 promoter may not be the mechanism for TMPRSS2 overexpression in PRAD tissues and PRAD pathogenesis. TMPRSS2 expresses eleven isoforms in PRAD tissues, with the TMPRSS2-001 isoform expressed highest and followed by TMPRSS2-201. Further isoform structures prediction showed that these two highly expressed isoforms have both SRCR_2 and Trypsin (Tryp_SPc) domains, which may be essential for TMPRSS2 functional roles for tumorigenesis and entry for SARS-CoV-2 in PRAD patients. Analyses of functional annotation and enrichment in TMPRSS2 showed that TMPRSS2 is mostly enriched in regulation of viral entry into host cells, protein processing and serine-type peptidase activity. TMPRSS2 is also associated with prostate gland cancer cell expression, different complex(es) formation, human influenza and carcinoma, pathways in prostate cancer, influenza A, and transcriptional misregulation in cancer. Altogether, even though high expression of TMPRSS2 may not be favourable for PRAD patient's survival, increased expression in these patients should play roles in susceptibility of the SARS-CoV-2 infection and clinical severity for COVID-19, highlighting the value of protective actions of PRAD cases by targeting or androgen-mediated therapeutic strategies in the COVID-19 pandemic.


Subject(s)
Adenocarcinoma/genetics , COVID-19/genetics , Genetic Predisposition to Disease/genetics , Prostatic Neoplasms/genetics , SARS-CoV-2/isolation & purification , Serine Endopeptidases/genetics , Adenocarcinoma/metabolism , COVID-19/metabolism , COVID-19/virology , DNA Methylation , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Gene Ontology , Humans , Kaplan-Meier Estimate , Male , Promoter Regions, Genetic/genetics , Prostate/metabolism , Prostatic Neoplasms/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Serine Endopeptidases/metabolism
2.
Mol Biol Rep ; 47(6): 4383-4392, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-260333

ABSTRACT

The ACE2 gene is a receptor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) for COVID-19 (coronavirus disease 2019). To analyze the expression profiles and clinical significances for this gene in humans, RNA-seq data representing 27 different tissues were analyzed using NCBI; total RNA was extracted from different tissues of mouse and semi-quantitative reverse transcriptional-polymerase chain reaction (Q-RT-PCR) was carried out. Immunohistochemistry expression profiles in normal tissues and cancer tissues and TCGA survival analysis in renal and liver cancer were conducted. ACE2 was highly conserved in different species. In normal tissues, ACE2 expression distributions were organ-specific, mainly in the kidney, male testis and female breast, and cardiovascular and gastrointestinal systems. High level of expression in testis, cardiovascular and gastrointestinal system indicated that SARS-CoV-2 might not only attack the lungs, but also affect other organs, particularly the testes, thus it may severely damage male sexual development for younger male and lead to infertility in an adult male, if he contracted COVID-19. On the other side, high expression of ACE2 was correlated with increased survival rate in renal and liver cancer, indicating that ACE2 is a prognostic marker in both renal cancer and liver cancers. Thus, the ACE2 is a functional receptor for SARS-CoV-2 and has a potential anti-tumor role in cancer. Taken together, this study may not only provide potential clues for further medical pathogenesis of COVID-19 and male fertility, but also indicate the clinical significance of the role of the ACE2 gene in cancer.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Kidney Neoplasms/genetics , Liver Neoplasms/genetics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/epidemiology , Receptors, Virus/genetics , Spike Glycoprotein, Coronavirus/genetics , Adult , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/drug effects , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/genetics , Databases, Genetic , Female , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Humans , Kidney/metabolism , Kidney/pathology , Kidney/virology , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Kidney Neoplasms/virology , Liver/metabolism , Liver/pathology , Liver/virology , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/virology , Lung/metabolism , Lung/pathology , Lung/virology , Male , Mammary Glands, Human/metabolism , Mammary Glands, Human/pathology , Mammary Glands, Human/virology , Mice , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/genetics , Protein Binding , Receptors, Virus/metabolism , SARS-CoV-2 , Sequence Analysis, RNA , Signal Transduction , Spike Glycoprotein, Coronavirus/metabolism , Survival Analysis , Testis/metabolism , Testis/pathology , Testis/virology
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