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2.
Chem Biol Interact ; 335: 109370, 2021 Feb 01.
Article in English | MEDLINE | ID: covidwho-1014379

ABSTRACT

The aberrant expression level of SARS-CoV-2 cell receptor gene ACE2 was reported in lung adenocarcinoma (LUAD) comorbidity of COVID-19. However, the association of ACE2 expression levels with immunosuppression and metabolic reprogramming in LUAD remains lacking. We investigated the expression level of ACE2, an association of ACE2 expression level with various types of immune signatures, immune ratios, and pathways. We employed a weighted gene co-expression network analysis (WGCNA) R package to identify the gene modules and investigated prognostic roles of hub genes in LUAD. Overexpression of ACE2 level was found in LUAD and ACE2 expression was negatively associated with various types of immune signatures including CD8+ T cells, CD4+ regulatory T cells, NK cells, and T cell activation. Besides, ACE2 upregulation was not only associated with CD8+ T cell/CD4+ regulatory T cell ratios but also linked with downregulation of immune-markers including CD8A, KLRC1, GZMA, GZMB, NKG7, CCL4, and IFNG. Moreover, the ACE2 expression level was found to be associated with the enrichment level of various metabolic pathways and it was also found that the metabolic pathways are directly positively correlated with the increased expression levels of ACE2, indicating that the overexpression of ACE2 is associated with metabolic reprogramming in LUAD. Furthermore, WGCNA based analysis revealed the gene modules in the high-ACE2-expression-level group of LUAD and identified GCLC and SLC7A11 hub genes which are not only highly expressed in lung adenocarcinoma but also correlated with the poor survival prognosis. Our analysis of ACE2 in LUAD tissues suggests that ACE2 is not only a receptor but is also associated with immunosuppression and metabolic reprogramming. This study underlines the clue for understanding the clinical significance of ACE2 in COVID-19 patients with LUAD comorbidity.


Subject(s)
Adenocarcinoma of Lung/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Immunity, Cellular/genetics , Immunity, Innate/genetics , Lung Neoplasms/metabolism , Adenocarcinoma of Lung/epidemiology , Amino Acid Transport System y+/genetics , Angiotensin-Converting Enzyme 2/genetics , COVID-19/epidemiology , Comorbidity , Computational Biology , Databases, Genetic/statistics & numerical data , Female , Gene Expression Regulation, Neoplastic , Glutamate-Cysteine Ligase/genetics , Humans , Lung Neoplasms/epidemiology , Lymphocyte Activation/genetics , Male , Non-Smokers , Protein Interaction Maps/genetics , SARS-CoV-2 , Smokers , T-Lymphocytes/metabolism , Transcriptome , Up-Regulation
3.
Nucleic Acids Res ; 49(D1): D183-D191, 2021 01 08.
Article in English | MEDLINE | ID: covidwho-873045

ABSTRACT

RNA molecules fold into complex structures that are important across many biological processes. Recent technological developments have enabled transcriptome-wide probing of RNA secondary structure using nucleases and chemical modifiers. These approaches have been widely applied to capture RNA secondary structure in many studies, but gathering and presenting such data from very different technologies in a comprehensive and accessible way has been challenging. Existing RNA structure probing databases usually focus on low-throughput or very specific datasets. Here, we present a comprehensive RNA structure probing database called RASP (RNA Atlas of Structure Probing) by collecting 161 deduplicated transcriptome-wide RNA secondary structure probing datasets from 38 papers. RASP covers 18 species across animals, plants, bacteria, fungi, and also viruses, and categorizes 18 experimental methods including DMS-seq, SHAPE-Seq, SHAPE-MaP, and icSHAPE, etc. Specially, RASP curates the up-to-date datasets of several RNA secondary structure probing studies for the RNA genome of SARS-CoV-2, the RNA virus that caused the on-going COVID-19 pandemic. RASP also provides a user-friendly interface to query, browse, and visualize RNA structure profiles, offering a shortcut to accessing RNA secondary structures grounded in experimental data. The database is freely available at http://rasp.zhanglab.net.


Subject(s)
Computational Biology/statistics & numerical data , Databases, Genetic/statistics & numerical data , High-Throughput Nucleotide Sequencing/statistics & numerical data , Nucleic Acid Conformation , RNA/chemistry , Transcriptome , Animals , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Computational Biology/methods , Genome, Viral/genetics , High-Throughput Nucleotide Sequencing/methods , Humans , Pandemics , RNA/genetics , RNA Probes/genetics , RNA, Bacterial/chemistry , RNA, Bacterial/genetics , RNA, Fungal/chemistry , RNA, Fungal/genetics , RNA, Plant/chemistry , RNA, Plant/genetics , RNA, Viral/chemistry , RNA, Viral/genetics , SARS-CoV-2/genetics , SARS-CoV-2/physiology
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