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1.
Life (Basel) ; 12(2)2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1686871

ABSTRACT

The current SARS-CoV-2 pandemic has emerged as an international challenge with strong medical and socioeconomic impact. The spectrum of clinical manifestations of SARS-CoV-2 is wide, covering asymptomatic or mild cases up to severe and life-threatening complications. Critical courses of SARS-CoV-2 infection are thought to be driven by the so-called "cytokine storm", derived from an excessive immune response that induces the release of proinflammatory cytokines and chemokines. In recent years, non-coding RNAs (ncRNAs) emerged as potential diagnostic and therapeutic biomarkers in both inflammatory and infectious diseases. Therefore, the identification of SARS-CoV-2 miRNAs and host miRNAs is an important research topic, investigating the host-virus crosstalk in COVID-19 infection, trying to answer the pressing question of whether miRNA-based therapeutics can be employed to tackle SARS-CoV-2 complications. In this review, we aimed to directly address ncRNA role in SARS-CoV-2-immune system crosstalk upon COVID-19 infection, particularly focusing on inflammatory pathways and cytokine storm syndromes.

2.
Fish Shellfish Immunol ; 120: 314-324, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1559895

ABSTRACT

Infectious hematopoietic necrosis virus (IHNV) is the vital pathogen that has caused the great economic loss in salmonid fisheries. To date, there is limited information concerning the changes of lncRNAs in RTG-2 cells infected by IHNV. In this study, a comparative transcriptome analysis of lncRNAs was performed in RTG-2 cells with and without IHNV infection to determine their changes and the effects on IHNV infection. The results showed that IHNV infection significantly changed the expression levels of lncRNAs and mRNAs, including 3693 differentially expressed lncRNAs (DE-lncRNAs) and 3503 differentially expressed mRNAs (DE-mRNAs) respectively. These DE-lncRNAs and DE-mRNAs induced by IHNV were mostly associated with immune response, RNA processing, and viral diseases related pathways. Further analysis found that some DE-lncRNAs might participate in the regulation of extracellular matrix metabolism, apoptosis, lipid synthesis, autophagy, and immune responses referring to the functions of their target genes. Afterwards, 349 co-expression relationships were constructed by 223 DE-lncRNAs and 271 DE-mRNAs, of which LTCONS_00146935 was the pivotal node in the interaction networks, and was together with its target genes modulated the immune responses under the IHNV infection. RT-qPCR results showed that the changes of the selected immune-related DEGs were in consistent with the RNA-seq data, suggesting that the sequencing data was relatively reliable. In summary, this is the first study to determine the changes and interactions of lncRNA-mRNA in RTG-2 cells under the IHNV infection. The results provided the valuable information concerning the lncRNAs in salmonid fish, which will benefit for future study on uncovering the roles of lncRNAs-mRNAs during the viral infection.


Subject(s)
Infectious hematopoietic necrosis virus , RNA, Long Noncoding , Rhabdoviridae Infections/veterinary , Transcriptome , Animals , Cell Line/virology , Fish Diseases/genetics , Fish Diseases/virology , Gene Expression Profiling/veterinary , Oncorhynchus mykiss , RNA, Long Noncoding/genetics , RNA, Messenger , RNA-Seq , Rhabdoviridae Infections/genetics
4.
Physiol Genomics ; 53(10): 433-440, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1398739

ABSTRACT

SARS-CoV-2 harbors many known unknown regions in the form of hypothetical open reading frames (ORFs). Although the mechanisms underlying the disease pathogenesis are not clearly understood, molecules such as long noncoding RNAs (lncRNAs) play a key regulatory role in the viral pathogenesis from endocytosis. We asked whether or not the lncRNAs in the host are associated with the viral proteins and argue that lncRNA-mRNAs molecules related to viral infection may regulate SARS-CoV-2 pathogenesis. Toward the end of the perspective, we provide challenges and insights into investigating these transgression pathways.


Subject(s)
COVID-19/genetics , Host-Pathogen Interactions/genetics , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , SARS-CoV-2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , COVID-19/virology , Epitopes , Female , Gene Expression Regulation , Humans , Male , Open Reading Frames , Phylogeny , Protein Interaction Maps , SARS-CoV-2/metabolism , Sex Factors
5.
Front Immunol ; 12: 700184, 2021.
Article in English | MEDLINE | ID: covidwho-1365542

ABSTRACT

Coronavirus disease 2019 (COVID-19), which has high incidence rates with rapid rate of transmission, is a pandemic that spread across the world, resulting in more than 3,000,000 deaths globally. Currently, several drugs have been used for the clinical treatment of COVID-19, such as antivirals (radecivir, baritinib), monoclonal antibodies (tocilizumab), and glucocorticoids (dexamethasone). Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are essential regulators of virus infections and antiviral immune responses including biological processes that are involved in the regulation of COVID-19 and subsequent disease states. Upon viral infections, cellular lncRNAs directly regulate viral genes and influence viral replication and pathology through virus-mediated changes in the host transcriptome. Additionally, several host lncRNAs could help the occurrence of viral immune escape by inhibiting type I interferons (IFN-1), while others could up-regulate IFN-1 production to play an antiviral role. Consequently, understanding the expression and function of lncRNAs during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection will provide insights into the development of lncRNA-based methods. In this review, we summarized the current findings of lncRNAs in the regulation of the strong inflammatory response, immune dysfunction and thrombosis induced by SARS-CoV-2 infection, discussed the underlying mechanisms, and highlighted the therapeutic challenges of COVID-19 treatment and its future research directions.


Subject(s)
COVID-19/immunology , Host Microbial Interactions/genetics , Immunity, Innate/genetics , RNA, Long Noncoding/metabolism , Thrombosis/immunology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Biomarkers/analysis , COVID-19/complications , COVID-19/drug therapy , COVID-19/genetics , COVID-19 Testing/methods , Cytokines/genetics , Cytokines/metabolism , Gene Expression Regulation, Viral/drug effects , Gene Expression Regulation, Viral/immunology , Host Microbial Interactions/drug effects , Host Microbial Interactions/immunology , Humans , Immune Evasion/genetics , Pandemics/prevention & control , RNA, Long Noncoding/analysis , RNA, Long Noncoding/antagonists & inhibitors , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Signal Transduction/genetics , Signal Transduction/immunology , Thrombosis/genetics , Thrombosis/virology , Virus Replication/drug effects , Virus Replication/genetics , Virus Replication/immunology
6.
Pharmaceuticals (Basel) ; 14(8)2021 Jul 30.
Article in English | MEDLINE | ID: covidwho-1335173

ABSTRACT

The present review describes COVID-19 severity in diabetes and diabetic kidney disease. We discuss the crucial effect of COVID-19-associated cytokine storm and linked injuries and associated severe mesenchymal activation in tubular epithelial cells, endothelial cells, and macrophages that influence neighboring cell homeostasis, resulting in severe proteinuria and organ fibrosis in diabetes. Altered microRNA expression disrupts cellular homeostasis and the renin-angiotensin-system, targets reno-protective signaling proteins, such as angiotensin-converting enzyme 2 (ACE2) and MAS1 receptor (MAS), and facilitates viral entry and replication in kidney cells. COVID-19-associated endotheliopathy that interacts with other cell types, such as neutrophils, platelets, and macrophages, is one factor that accelerates prethrombotic reactions and thrombus formation, resulting in organ failures in diabetes. Apart from targeting vital signaling through ACE2 and MAS, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are also associated with higher profibrotic dipeptidyl transferase-4 (DPP-4)-mediated mechanisms and suppression of AMP-activated protein kinase (AMPK) activation in kidney cells. Lowered DPP-4 levels and restoration of AMPK levels are organ-protective, suggesting a pathogenic role of DPP-4 and a protective role of AMPK in diabetic COVID-19 patients. In addition to standard care provided to COVID-19 patients, we urgently need novel drug therapies that support the stability and function of both organs and cell types in diabetes.

7.
Cancer Cell Int ; 21(1): 278, 2021 May 25.
Article in English | MEDLINE | ID: covidwho-1243810

ABSTRACT

Epstein Barr-virus (EBV) is related to several cancers. Long non-coding RNAs (lncRNAs) act by regulating target genes and are involved in tumourigenesis. However, the role of lncRNAs in EBV-associated cancers is rarely reported. Understanding the role and mechanism of lncRNAs in EBV-associated cancers may contribute to diagnosis, prognosis and clinical therapy in the future. EBV encodes not only miRNAs, but also BART lncRNAs during latency and the BHLF1 lncRNA during both the latent and lytic phases. These lncRNAs can be targeted regulate inflammation, invasion, and migration and thus tumourigenesis. The products of EBV also directly and indirectly regulate host lncRNAs, including LINC00312, NORAD CYTOR, SHNG8, SHNG5, MINCR, lncRNA-BC200, LINC00672, MALATI1, LINC00982, LINC02067, IGFBP7-AS1, LOC100505716, LOC100128494, NAG7 and RP4-794H19.1, to facilitate tumourigenesis using different mechanisms. Additionally, lncRNAs have been previously validated to interact with microRNAs (miRNAs), and lncRNAs and miRNAs mutually suppress each other. The EBV-miR-BART6-3p/LOC553103/STMN1 axis inhibits EBV-associated tumour cell proliferation. Additionally, H. pylori-EBV co-infection promotes inflammatory lesions and results in EMT. HPV-EBV co-infection inhibits the transition from latency to lytic replication. KSHV-EBV co-infection aggravates tumourigenesis in huNSG mice. COVID-19-EBV co-infection may activate the immune system to destroy a tumour, although this situation is rare and the mechanism requires further confirmation. Hopefully, this information will shed some light on tumour therapy strategies tumourigenesis. Additionally, this strategy benefits for infected patients by preventing latency to lytic replication. Understanding the role and expression of lnRNAs in these two phases of EBV is critical to control the transition from latency to the lytic replication phase. This review presents differential expressed lncRNAs in EBV-associated cancers and provides resources to aid in developing superior strategies for clinical therapy.

8.
EPMA J ; 11(2): 289-309, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1086691

ABSTRACT

RELEVANCE: Ivermectin, as an old anti-parasite drug, can suppress almost completely the growth of various human cancers, including ovarian cancer (OC). However, its anticancer mechanism remained to be further studied at the molecular levels. Ivermectin-related molecule-panel changes will serve a useful tool for its personalized drug therapy and prognostic assessment in OCs. PURPOSE: To explore the functional significance of ivermectin-mediated lncRNA-EIF4A3-mRNA axes in OCs and ivermectin-related molecule-panel for its personalized drug therapy monitoring. METHODS: Based on our previous study, a total of 16 lncRNA expression patterns were analyzed using qRT-PCR before and after ivermectin-treated different OC cell lines (TOV-21G and A2780). Stable isotope labeling with amino acids in cell culture (SILAC)-based quantitative proteomics was used to analyze the protein expressions of EIF4A3 and EIF4A3-binding mRNAs in ovarian cancer cells treated with and without ivermectin. A total of 411 OC patients from the Cancer Genome Atlas (TCGA) database with the selected lncRNA expressions and the corresponding clinical data were included. Lasso regression was constructed to examine the relationship between lncRNA signature and OC survival risk. The overall survival analysis between high-risk and low-risk groups used the Kaplan-Meier method. Heatmap showed the correlation between risk groups and clinical characteristics. The univariate and multivariate models were established with Cox regression. RESULTS: SILAC-based quantitative proteomics found the protein expression levels of EIF4A3 and 116 EIF4A3-binding mRNAs were inhibited by ivermectin in OC cells. Among the analyzed 16 lncRNAs (HCG15, KIF9-AS1, PDCD4-AS1, ZNF674-AS1, ZNRF3-AS1, SOS1-IT1, LINC00565, SNHG3, PLCH1-AS1, WWTR1-AS1, LINC00517, AL109767.1, STARD13-IT1, LBX2-AS1, LEMD1-AS1, and HOXC-AS3), only 7 lncRNAs (HCG15, KIF9-AS1, PDCD4-AS1, ZNF674-AS1, ZNRF3-AS1, SOS1-IT1, and LINC00565) were obtained for further lasso regression when combined with the results of drug testing and overall survival analysis. Lasso regression identified the prognostic model of ivermectin-related three-lncRNA signature (ZNRF3-AS1, SOS1-IT1, and LINC00565). The high-risk and low-risk groups based on the prognostic model were significantly related to overall survival and clinicopathologic characteristics (survival status, lymphatic invasion, cancer status, and clinical stage) in OC patients and remained independent risk factors according to multivariate COX analysis (p < 0.05). CONCLUSION: Those findings provided the potential targeted lncRNA-EIF4A3-mRNA pathways of ivermectin in OC, and constructed the effective prognostic model, which benefits discovery of novel mechanism of ivermectin to suppress ovarian cancer cells, and the ivermectin-related molecule-panel changes benefit for its personalized drug therapy and prognostic assessment towards its predictive, preventive, and personalized medicine (PPPM) in OCs.

9.
J Biomol Struct Dyn ; 40(8): 3681-3696, 2022 May.
Article in English | MEDLINE | ID: covidwho-965123

ABSTRACT

The coronavirus disease, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global health crisis that is being endured with an increased alarm of transmission each day. Though the pandemic has activated innumerable research attention to decipher an antidote, fundamental understanding of the molecular mechanisms is necessary to halt the disease progression. The study focused on comparison of the COVID-19 infected lung tissue gene expression datasets -GSE155241 and GSE150316 with the GEO2R-limma package. The significant up- and downregulated genes were annotated. Further evaluation of the enriched pathways, transcription factors, kinases, noncoding RNAs and drug perturbations revealed the significant molecular mechanisms of the host response. The results revealed a surge in mitochondrial respiration, cytokines, neurodegenerative mechanisms and deprived oxygen, iron, copper, and glucose transport. Hijack of ubiquitination by SARS-CoV-2, hox gene differentiation, histone modification, and miRNA biogenesis were the notable molecular mechanisms inferred. Long non-coding RNAs such as C058791.1, TTTY15 and TPTEP1 were predicted to be efficient in regulating the disease mechanisms. Drugs-F-1566-0341, Digoxin, Proscillaridin and Linifanib that reverse the gene expression signatures were predicted from drug perturbations analysis. The binding efficiency and interaction of proscillaridin and digoxin as obtained from the molecular docking studies confirmed their therapeutic potential. Two overlapping upregulated genes MDH1, SGCE and one downregulated gene PFKFB3 were appraised as potential biomarkers candidates. The upregulation of PGM5, ISLR and ANK2 as measured from their expressions in normal lungs affirmed their possible prognostic biomarker competence. The study explored significant insights for better diagnosis, and therapeutic options for COVID-19. Communicated by Ramaswamy H. Sarma.


Subject(s)
COVID-19 , MicroRNAs , Proscillaridin , Biomarkers , COVID-19/drug therapy , COVID-19/genetics , Digoxin , Gene Expression Profiling , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Molecular Docking Simulation , SARS-CoV-2/genetics
10.
Genes (Basel) ; 11(7)2020 07 07.
Article in English | MEDLINE | ID: covidwho-640013

ABSTRACT

The global spread of COVID-19, caused by pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for an imminent response from medical research communities to better understand this rapidly spreading infection. Employing multiple bioinformatics and computational pipelines on transcriptome data from primary normal human bronchial epithelial cells (NHBE) during SARS-CoV-2 infection revealed activation of several mechanistic networks, including those involved in immunoglobulin G (IgG) and interferon lambda (IFNL) in host cells. Induction of acute inflammatory response and activation of tumor necrosis factor (TNF) was prominent in SARS-CoV-2 infected NHBE cells. Additionally, disease and functional analysis employing ingenuity pathway analysis (IPA) revealed activation of functional categories related to cell death, while those associated with viral infection and replication were suppressed. Several interferon (IFN) responsive gene targets (IRF9, IFIT1, IFIT2, IFIT3, IFITM1, MX1, OAS2, OAS3, IFI44 and IFI44L) were highly upregulated in SARS-CoV-2 infected NBHE cell, implying activation of antiviral IFN innate response. Gene ontology and functional annotation of differently expressed genes in patient lung tissues with COVID-19 revealed activation of antiviral response as the hallmark. Mechanistic network analysis in IPA identified 14 common activated, and 9 common suppressed networks in patient tissue, as well as in the NHBE cell model, suggesting a plausible role for these upstream regulator networks in the pathogenesis of COVID-19. Our data revealed expression of several viral proteins in vitro and in patient-derived tissue, while several host-derived long noncoding RNAs (lncRNAs) were identified. Our data highlights activation of IFN response as the main hallmark associated with SARS-CoV-2 infection in vitro and in human, and identified several differentially expressed lncRNAs during the course of infection, which could serve as disease biomarkers, while their precise role in the host response to SARS-CoV-2 remains to be investigated.


Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , RNA, Long Noncoding/metabolism , Viral Proteins/metabolism , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , Biomarkers/metabolism , Bronchi/cytology , COVID-19 , Cell Death , Cell Line , Cluster Analysis , Coronavirus Infections/genetics , Coronavirus Infections/virology , Epithelial Cells/cytology , Epithelial Cells/virology , Gene Regulatory Networks , Humans , Immunity, Innate , Interferon-Stimulated Gene Factor 3, gamma Subunit/genetics , Lung/metabolism , Lung/pathology , Lung/virology , Pandemics , Pneumonia, Viral/genetics , Pneumonia, Viral/virology , RNA, Long Noncoding/genetics , SARS-CoV-2 , Transcriptome
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