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1.
Cells ; 11(22)2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2199805

ABSTRACT

Long Intergenic Non-Protein Coding RNA 665 (LINC00665) is an RNA gene located on the minus strand of chromosome 19. This lncRNA acts as a competing endogenous RNA for miR-4458, miR-379-5p, miR-551b-5p, miR-3619-5p, miR-424-5p, miR-9-5p, miR-214-3p, miR-126-5p, miR-149-3p, miR-379-5p, miR-665, miR-34a-5p, miR-186-5p, miR-138-5p, miR-181c-5p, miR-98, miR-195-5p, miR-224-5p, miR-3619, miR-708, miR-101, miR-1224-5p, miR-34a-5p, and miR-142-5p. Via influencing expression of these miRNAs, it can enhance expression of a number of oncogenes. Moreover, LINC00665 can influence activity of Wnt/ß-Catenin, TGF-ß, MAPK1, NF-κB, ERK, and PI3K/AKT signaling. Function of this lncRNA has been assessed through gain-of-function tests and/or loss-of-function studies. Furthermore, diverse research groups have evaluated its expression levels in tissue samples using microarray and RT-qPCR techniques. In this manuscript, we have summarized the results of these studies and categorized them in three sections, i.e., cell line studies, animal studies, and investigations in clinical samples.


Subject(s)
MicroRNAs , Neoplasms , RNA, Long Noncoding , Animals , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Phosphatidylinositol 3-Kinases/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasms/genetics , Signal Transduction/genetics
2.
Cells ; 11(21)2022 Oct 25.
Article in English | MEDLINE | ID: covidwho-2199804

ABSTRACT

Extracellular vesicles (EVs) are small lipid bilayer-delimited particles that are naturally released from cells into body fluids, and therefore can travel and convey regulatory functions in the distal parts of the body. EVs can transmit paracrine signaling by carrying over cytokines, chemokines, growth factors, interleukins (ILs), transcription factors, and nucleic acids such as DNA, mRNAs, microRNAs, piRNAs, lncRNAs, sn/snoRNAs, mtRNAs and circRNAs; these EVs travel to predecided destinations to perform their functions. While mesenchymal stem cells (MSCs) have been shown to improve healing and facilitate treatments of various diseases, the allogenic use of these cells is often accompanied by serious adverse effects after transplantation. MSC-produced EVs are less immunogenic and can serve as an alternative to cellular therapies by transmitting signaling or delivering biomaterials to diseased areas of the body. This review article is focused on understanding the properties of EVs derived from different types of MSCs and MSC-EV-based therapeutic options. The potential of modern technologies such as 3D bioprinting to advance EV-based therapies is also discussed.


Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , MicroRNAs , Extracellular Vesicles/metabolism , Mesenchymal Stem Cells/metabolism , Cell- and Tissue-Based Therapy , MicroRNAs/genetics , MicroRNAs/metabolism , Bioengineering
3.
Cells ; 11(22)2022 Nov 18.
Article in English | MEDLINE | ID: covidwho-2142562

ABSTRACT

Firstly, I apologize for the delayed publication of this Special Issue in the form of a book title [...].


Subject(s)
Computational Biology , MicroRNAs , MicroRNAs/genetics
4.
Front Immunol ; 13: 1001070, 2022.
Article in English | MEDLINE | ID: covidwho-2142020

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) is the causative virus of the pandemic coronavirus disease 2019 (COVID-19). Evaluating the immunological factors and other implicated processes underlying the progression of COVID-19 is essential for the recognition and then the design of efficacious therapies. Therefore, we analyzed RNAseq data obtained from PBMCs of the COVID-19 patients to explore coding and non-coding RNA diagnostic immunological panels. For this purpose, we integrated multiple RNAseq data and analyzed them overall as well as by considering the state of disease including severe and non-severe conditions. Afterward, we utilized a co-expressed-based machine learning procedure comprising weighted-gene co-expression analysis and differential expression gene as filter phase and recursive feature elimination-support vector machine as wrapper phase. This procedure led to the identification of two modules containing 5 and 84 genes which are mostly involved in cell dysregulation and innate immune suppression, respectively. Moreover, the role of vitamin D in regulating some classifiers was highlighted. Further analysis disclosed the role of discriminant miRNAs including miR-197-3p, miR-150-5p, miR-340-5p, miR-122-5p, miR-1307-3p, miR-34a-5p, miR-98-5p and their target genes comprising GAN, VWC2, TNFRSF6B, and CHST3 in the metabolic pathways. These classifiers differentiate the final fate of infection toward severe or non-severe COVID-19. The identified classifier genes and miRNAs may help in the proper design of therapeutic procedures considering their involvement in the immune and metabolic pathways.


Subject(s)
COVID-19 , MicroRNAs , Humans , COVID-19/diagnosis , COVID-19/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , SARS-CoV-2/genetics , Machine Learning
5.
Front Immunol ; 13: 1008084, 2022.
Article in English | MEDLINE | ID: covidwho-2119705

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global pandemic, resulting in great fatalities around the world. Although the antiviral roles of RNA interference (RNAi) have been well studied in plants, nematodes and insects, the antiviral roles of RNAi in mammalians are still debating as RNAi effect is suspected to be suppressed by interferon (IFN) signaling pathways in most cell types. To determine the role of RNAi in mammalian resistance to SARS-CoV-2, we studied the profiling of host small RNAs and SARS-CoV-2 virus-derived small RNAs (vsRNAs) in the early infection stages of Vero cells, an IFN-deficient cell line. We found that host microRNAs (miRNAs) were dysregulated upon SARS-CoV-2 infection, resulting in downregulation of microRNAs playing antiviral functions and upregulation of microRNAs facilitating viral proliferations. Moreover, vsRNA peaked at 22 nt at negative strand but not the positive strand of SARS-CoV-2 and formed successive Dicer-spliced pattern at both strands. Similar characteristics of vsRNAs were observed in IFN-deficient cell lines infected with Sindbis and Zika viruses. Together, these findings indicate that host cell may deploy RNAi pathway to combat SARS-CoV-2 infection in IFN-deficient cells, informing the alternative antiviral strategies to be developed for patients or tissues with IFN deficiency.


Subject(s)
COVID-19 , MicroRNAs , Zika Virus Infection , Zika Virus , Chlorocebus aethiops , Animals , Humans , Vero Cells , SARS-CoV-2/genetics , RNA, Viral/genetics , COVID-19/genetics , MicroRNAs/genetics , Antiviral Agents , Mammals
6.
Eur J Med Res ; 27(1): 251, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2115714

ABSTRACT

BACKGROUND: Patients with non-alcoholic fatty liver disease (NAFLD) may be more susceptible to coronavirus disease 2019 (COVID-19) and even more likely to suffer from severe COVID-19. Whether there is a common molecular pathological basis for COVID-19 and NAFLD remains to be identified. The present study aimed to elucidate the transcriptional alterations shared by COVID-19 and NAFLD and to identify potential compounds targeting both diseases. METHODS: Differentially expressed genes (DEGs) for COVID-19 and NAFLD were extracted from the GSE147507 and GSE89632 datasets, and common DEGs were identified using the Venn diagram. Subsequently, we constructed a protein-protein interaction (PPI) network based on the common DEGs and extracted hub genes. Then, we performed gene ontology (GO) and pathway analysis of common DEGs. In addition, transcription factors (TFs) and miRNAs regulatory networks were constructed, and drug candidates were identified. RESULTS: We identified a total of 62 common DEGs for COVID-19 and NAFLD. The 10 hub genes extracted based on the PPI network were IL6, IL1B, PTGS2, JUN, FOS, ATF3, SOCS3, CSF3, NFKB2, and HBEGF. In addition, we also constructed TFs-DEGs, miRNAs-DEGs, and protein-drug interaction networks, demonstrating the complex regulatory relationships of common DEGs. CONCLUSION: We successfully extracted 10 hub genes that could be used as novel therapeutic targets for COVID-19 and NAFLD. In addition, based on common DEGs, we propose some potential drugs that may benefit patients with COVID-19 and NAFLD.


Subject(s)
COVID-19 , MicroRNAs , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Gene Regulatory Networks , Systems Biology , Gene Expression Profiling , Computational Biology , COVID-19/genetics , MicroRNAs/genetics
7.
J Vis Exp ; (188)2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2110320

ABSTRACT

Circular RNAs (circRNAs) are a class of non-coding RNAs that are formed via back-splicing. These circRNAs are predominantly studied for their roles as regulators of various biological processes. Notably, emerging evidence demonstrates that host circRNAs can be differentially expressed (DE) upon infection with pathogens (e.g., influenza and coronaviruses), suggesting a role for circRNAs in regulating host innate immune responses. However, investigations on the role of circRNAs during pathogenic infections are limited by the knowledge and skills required to carry out the necessary bioinformatic analysis to identify DE circRNAs from RNA sequencing (RNA-seq) data. Bioinformatics prediction and identification of circRNAs is crucial before any verification, and functional studies using costly and time-consuming wet-lab techniques. To solve this issue, a step-by-step protocol of in silico prediction and characterization of circRNAs using RNA-seq data is provided in this manuscript. The protocol can be divided into four steps: 1) Prediction and quantification of DE circRNAs via the CIRIquant pipeline; 2) Annotation via circBase and characterization of DE circRNAs; 3) CircRNA-miRNA interaction prediction through Circr pipeline; 4) functional enrichment analysis of circRNA parental genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). This pipeline will be useful in driving future in vitro and in vivo research to further unravel the role of circRNAs in host-pathogen interactions.


Subject(s)
MicroRNAs , RNA, Circular , RNA, Circular/genetics , Sequence Analysis, RNA , MicroRNAs/genetics , Computational Biology/methods , Host-Pathogen Interactions/genetics , Gene Expression Profiling/methods
8.
Int J Mol Sci ; 23(22)2022 Nov 09.
Article in English | MEDLINE | ID: covidwho-2110129

ABSTRACT

This review explored the role of vascular endothelial growth factor receptor-2 (VEGFR-2) in the synergy of preeclampsia (PE), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Downregulation of VEGFR-2 in PE promotes endothelial dysfunction and prevents endothelial cell (EC) migration, proliferation, and differentiation. The HIV-1 accessory protein, tat (trans-activator of transcription), prevents VEGFR-2 signaling via the vascular endothelial growth factor A (VEGF-A) ligand. Combined antiretroviral therapy (cART) may cause immune reconstitution, impaired decidualization, and endothelial injury, thus may be a risk factor for PE development. The VEGF/VEGFR-2 interaction may be associated with SARS-CoV-2-related pulmonary oedema. Endothelial dysfunction and heightened inflammation are both associated with PE, HIV, and SARS-CoV-2 infection; therefore, it is plausible that both characteristics may be exacerbated in the synergy of these events. In addition, this review explored microRNAs (miR) regulating VEGFR-2. An overexpression of miR-126 is evident in PE, HIV, and SARS-CoV-2 infection; thus, modulating the expression of miR-126 may be a therapeutic strategy. However, the involvement of microRNAs in PE, HIV, and SARS-CoV-2 infection needs further investigating. Since these conditions have been evaluated independently, this review attempts to predict their clinical manifestations in their synergy, as well as independently; thereby providing a platform for early diagnosis and therapeutic potential in PE, HIV, and SARS-CoV-2 infection.


Subject(s)
COVID-19 , HIV Infections , MicroRNAs , Pre-Eclampsia , Female , Humans , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor A/genetics , COVID-19/complications , COVID-19/drug therapy , SARS-CoV-2 , HIV Infections/complications , HIV Infections/drug therapy , Comorbidity , MicroRNAs/genetics , HIV
9.
BMC Med Genomics ; 15(Suppl 2): 94, 2022 04 23.
Article in English | MEDLINE | ID: covidwho-2089198

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNA that can downregulate their targets by selectively binding to the 3' untranslated region (3'UTR) of most messenger RNAs (mRNAs) in the human genome. MiRNAs can interact with other molecules such as viruses and act as a mediator for viral infection. In this study, we examined whether, and to what extent, the SARS-CoV-2 virus can serve as a "sponge" for human miRNAs. RESULTS: We identified multiple potential miRNA/target pairs that may be disrupted during SARS-CoV-2 infection. Using miRNA expression profiles and RNA-seq from published studies, we further identified a highly confident list of 5 miRNA/target pairs that could be disrupted by the virus's miRNA sponge effect, namely hsa-miR-374a-5p/APOL6, hsa-let-7f-1-3p/EIF4A2, hsa-miR-374a-3p/PARP11, hsa-miR-548d-3p/PSMA2 and hsa-miR-23b-3p/ZNFX1 pairs. Using single-cell RNA-sequencing based data, we identified two important miRNAs, hsa-miR-302c-5p and hsa-miR-16-5p, to be potential virus targeting miRNAs across multiple cell types from bronchoalveolar lavage fluid samples. We further validated some of our findings using miRNA and gene enrichment analyses and the results confirmed with findings from previous studies that some of these identified miRNA/target pairs are involved in ACE2 receptor network, regulating pro-inflammatory cytokines and in immune cell maturation and differentiation. CONCLUSION: Using publicly available databases and patient-related expression data, we found that acting as a "miRNA sponge" could be one explanation for SARS-CoV-2-mediated pathophysiological changes. This study provides a novel way of utilizing SARS-CoV-2 related data, with bioinformatics approaches, to help us better understand the etiology of the disease and its differential manifestation across individuals.


Subject(s)
COVID-19 , MicroRNAs , SARS-CoV-2 , 3' Untranslated Regions , COVID-19/genetics , Computational Biology/methods , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Messenger/genetics , SARS-CoV-2/genetics , SARS-CoV-2/metabolism
10.
Dokl Biochem Biophys ; 506(1): 206-209, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2088454

ABSTRACT

In the present manuscript we analyzed the influence of hypoxic response in Caco-2 cells on the expression of genes and miRNAs involved in the mechanisms of intracellular transport of SARS-CoV-2 viral particles, especially endocytosis and transcytosis. With the use of RNA sequencing of Caco-2 cells treated with hypoxia-inducing oxyquinoline derivative, we showed two-fold increase in the expression of the main SARS-CoV-2 receptor ACE2. Expression of the non-canonical receptor TFRC was also elevated. We also observed a significant increase in the expression levels of genes from the low-density lipoprotein (LDL) receptor family, which play a crucial role in the transcytosis: LDLR, LRP1, LRP4, and LRP5. Upregulation of LDLR was coupled with the downregulation of hsa-miR-148a-3p, which can directly bind to LDLR mRNA. Thus, the hypoxic response in Caco-2 cells includes upregulation of genes involved in the mechanisms of endocytosis and transcytosis of SARS-CoV-2 viral particles.


Subject(s)
COVID-19 , Cell Hypoxia , Endocytosis , Transcytosis , Humans , Caco-2 Cells , MicroRNAs/genetics , SARS-CoV-2
11.
Molecules ; 27(19)2022 Oct 09.
Article in English | MEDLINE | ID: covidwho-2066288

ABSTRACT

With the increasing understanding of various disease-related noncoding RNAs, ncRNAs are emerging as novel drugs and drug targets. Nucleic acid drugs based on different types of noncoding RNAs have been designed and tested. Chemical modification has been applied to noncoding RNAs such as siRNA or miRNA to increase the resistance to degradation with minimum influence on their biological function. Chemical biological methods have also been developed to regulate relevant noncoding RNAs in the occurrence of various diseases. New strategies such as designing ribonuclease targeting chimeras to degrade endogenous noncoding RNAs are emerging as promising approaches to regulate gene expressions, serving as next-generation drugs. This review summarized the current state of noncoding RNA-based theranostics, major chemical modifications of noncoding RNAs to develop nucleic acid drugs, conjugation of RNA with different functional biomolecules as well as design and screening of potential molecules to regulate the expression or activity of endogenous noncoding RNAs for drug development. Finally, strategies of improving the delivery of noncoding RNAs are discussed.


Subject(s)
MicroRNAs , RNA, Untranslated , MicroRNAs/genetics , MicroRNAs/metabolism , Pharmaceutical Preparations , RNA, Small Interfering/genetics , RNA, Untranslated/genetics , Ribonucleases
12.
Front Immunol ; 13: 988479, 2022.
Article in English | MEDLINE | ID: covidwho-2065517

ABSTRACT

Background: The coronavirus disease (COVID-19) pandemic has posed a significant challenge for global health systems. Increasing evidence shows that asthma phenotypes and comorbidities are major risk factors for COVID-19 symptom severity. However, the molecular mechanisms underlying the association between COVID-19 and asthma are poorly understood. Therefore, we conducted bioinformatics and systems biology analysis to identify common pathways and molecular biomarkers in patients with COVID-19 and asthma, as well as potential molecular mechanisms and candidate drugs for treating patients with both COVID-19 and asthma. Methods: Two sets of differentially expressed genes (DEGs) from the GSE171110 and GSE143192 datasets were intersected to identify common hub genes, shared pathways, and candidate drugs. In addition, murine models were utilized to explore the expression levels and associations of the hub genes in asthma and lung inflammation/injury. Results: We discovered 157 common DEGs between the asthma and COVID-19 datasets. A protein-protein-interaction network was built using various combinatorial statistical approaches and bioinformatics tools, which revealed several hub genes and critical modules. Six of the hub genes were markedly elevated in murine asthmatic lungs and were positively associated with IL-5, IL-13 and MUC5AC, which are the key mediators of allergic asthma. Gene Ontology and pathway analysis revealed common associations between asthma and COVID-19 progression. Finally, we identified transcription factor-gene interactions, DEG-microRNA coregulatory networks, and potential drug and chemical-compound interactions using the hub genes. Conclusion: We identified the top 15 hub genes that can be used as novel biomarkers of COVID-19 and asthma and discovered several promising candidate drugs that might be helpful for treating patients with COVID-19 and asthma.


Subject(s)
Asthma , COVID-19 , MicroRNAs , Animals , Asthma/genetics , Biomarkers, Tumor/genetics , COVID-19/genetics , Computational Biology , Gene Expression Profiling , Gene Regulatory Networks , Interleukin-13/genetics , Interleukin-5/genetics , Mice , MicroRNAs/genetics , Systems Biology , Transcription Factors/genetics
13.
Brief Bioinform ; 23(6)2022 Nov 19.
Article in English | MEDLINE | ID: covidwho-2062859

ABSTRACT

MOTIVATION: Single-cell/nuclei RNA-sequencing (scRNA-seq) technologies can simultaneously quantify gene expression in thousands of cells across the genome. However, the majority of the noncoding RNAs, such as microRNAs (miRNAs), cannot currently be profiled at the same scale. MiRNAs are a class of small noncoding RNAs and play an important role in gene regulation. MiRNAs originate from the processing of primary transcripts, known as primary-microRNAs (pri-miRNAs). The pri-miRNA transcripts, independent of their cognate miRNAs, can also function as long noncoding RNAs, code for micropeptides or even interact with DNA, acting like enhancers. Therefore, it is apparent that the significance of scRNA-seq pri-miRNA profiling expands beyond using pri-miRNA as proxies of mature miRNAs. However, there are no computational methods that allow profiling and quantification of pri-miRNAs at the single-cell-type resolution. RESULTS: We have developed a simple yet effective computational framework to profile pri-MiRNAs from single-cell RNA-sequencing datasets (PPMS). Based on user input, PPMS can profile pri-miRNAs at cell-type resolution. PPMS can be applied to both newly produced and publicly available datasets obtained via single cell or single-nuclei RNA-seq. It allows users to (i) investigate the distribution of pri-miRNAs across cell types and cell states and (ii) establish a relationship between the number of cells/reads sequenced and the detection of pri-miRNAs. Here, to demonstrate its efficacy, we have applied PPMS to publicly available scRNA-seq data generated from (i) individual chambers (ventricles and atria) of the human heart, (ii) human pluripotent stem cells during their differentiation into cardiomyocytes (the heart beating cells) and (iii) hiPSCs-derived cardiomyocytes infected with severe acute respiratory syndrome coronavirus 2.


Subject(s)
COVID-19 , MicroRNAs , RNA, Small Untranslated , Humans , RNA Processing, Post-Transcriptional , Gene Expression Regulation , MicroRNAs/genetics , MicroRNAs/metabolism
14.
Hypertens Res ; 45(10): 1582-1598, 2022 10.
Article in English | MEDLINE | ID: covidwho-2062199

ABSTRACT

Renalase is a ~38 kDa flavin-adenine dinucleotide (FAD) domain-containing protein that can function as a cytokine and an anomerase. It is emerging as a novel regulator of cardiometabolic diseases. Expressed mainly in the kidneys, renalase has been reported to have a hypotensive effect and may control blood pressure through regulation of sympathetic tone. Furthermore, genetic variations in the renalase gene, such as a functional missense polymorphism (Glu37Asp), have implications in the cardiovascular and renal systems and can potentially increase the risk of cardiometabolic disorders. Research on the physiological functions and biochemical actions of renalase over the years has indicated a role for renalase as one of the key proteins involved in various disease states, such as diabetes, impaired lipid metabolism, and cancer. Recent studies have identified three transcription factors (viz., Sp1, STAT3, and ZBP89) as key positive regulators in modulating the expression of the human renalase gene. Moreover, renalase is under the post-transcriptional regulation of two microRNAs (viz., miR-29b, and miR-146a), which downregulate renalase expression. While renalase supplementation may be useful for treating hypertension, inhibition of renalase signaling may be beneficial to patients with cancerous tumors. However, more incisive investigations are required to unravel the potential therapeutic applications of renalase. Based on the literature pertaining to the function and physiology of renalase, this review attempts to consolidate and comprehend the role of renalase in regulating cardiometabolic and renal disorders.


Subject(s)
Hypertension , Kidney Diseases , MicroRNAs , Humans , Hypertension/genetics , Kidney Diseases/genetics , MicroRNAs/genetics , Monoamine Oxidase/genetics , Monoamine Oxidase/metabolism
15.
Viruses ; 14(9)2022 09 02.
Article in English | MEDLINE | ID: covidwho-2055390

ABSTRACT

Only two decades after discovering miRNAs, our understanding of the functional effects of deregulated miRNAs in the development of diseases, particularly cancer, has been rapidly evolving. These observations and functional studies provide the basis for developing miRNA-based diagnostic markers or new therapeutic strategies. Adenoviral (Ad) vectors belong to the most frequently used vector types in gene therapy and are suitable for strong short-term transgene expression in a variety of cells. Here, we report the set-up and functionality of an Ad-based miRNA vector platform that can be employed to deliver and express a high level of miRNAs efficiently. This vector platform allows fast and efficient vector production to high titers and the expression of pri-miRNA precursors under the control of a polymerase II promoter. In contrast to non-viral miRNA delivery systems, this Ad-based miRNA vector platform allows accurate dosing of the delivered miRNAs. Using a two-vector model, we showed that Ad-driven miRNA expression was sufficient in down-regulating the expression of an overexpressed and highly stable protein. Additional data corroborated the downregulation of multiple endogenous target RNAs using the system presented here. Additionally, we report some unanticipated synergistic effects on the transduction efficiencies in vitro when cells were consecutively transduced with two different Ad-vectors. This effect might be taken into consideration for protocols using two or more different Ad vectors simultaneously.


Subject(s)
MicroRNAs , Adenoviridae/genetics , Adenoviridae/metabolism , Genetic Therapy/methods , Genetic Vectors/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Transgenes
16.
J Clin Lab Anal ; 36(11): e24672, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2047648

ABSTRACT

BACKGROUND: The pandemic COVID-19 has caused a high mortality rate and poses a significant threat to the population of the entire world. Due to the novelty of this disease, the pathogenic mechanism of the disease and the host cell's response are not yet fully known, so lack of evidence prevents a definitive conclusion about treatment strategies. The current study employed a small RNA deep-sequencing approach for screening differentially expressed microRNA (miRNA) in blood and bronchoalveolar fluid (BALF) samples of acute respiratory distress syndrome (ARDS) patients. METHODS: In this study, BALF and blood samples were taken from patients with ARDS (n = 5). Control samples were those with suspected lung cancer candidates for lung biopsy (n = 3). Illumina high-throughput (HiSeq 2000) sequencing was performed to identify known and novel miRNAs differentially expressed in the blood and BALFs of ARDS patients compared with controls. RESULTS: Results showed 2234 and 8324 miRNAs were differentially expressed in blood and BALF samples, respectively. In BALF samples, miR-282, miR-15-5p, miR-4485-3p, miR-483-3p, miR-6891-5p, miR-200c, miR-4463, miR-483-5p, and miR-98-5p were upregulated and miR-15a-5p, miR-548c-5p, miR-548d-3p, miR-365a-3p, miR-3939, miR-514-b-5p, miR-513a-3p, miR-513a-5p, miR-664a-3p, and miR-766-3p were downregulated. On the contrary, in blood samples miR-15b-5p, miR-18a-3p, miR-486-3p, miR-486-5p, miR-146a-5p, miR-16-2-3p, miR-6501-5p, miR-365-3p, miR-618, and miR-623 were top upregulated miRNAs and miR-21-5p, miR-142a-3p, miR-181-a, miR-31-5p, miR-99-5p, miR-342-5p, miR-183-5p, miR-627-5p, and miR-144-3p were downregulated miRNAs. Network functional analysis for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), in ARDS patients' blood and BALF samples, showed that the target genes were more involved in activating inflammatory and apoptosis process. CONCLUSION: Based on our results, the transcriptome profile of ARDS patients would be a valuable source for understanding molecular mechanisms of host response and developing clinical guidance on anti-inflammatory medication.


Subject(s)
COVID-19 , MicroRNAs , Respiratory Distress Syndrome , Humans , MicroRNAs/genetics , COVID-19/genetics , Sequence Analysis, RNA/methods , High-Throughput Nucleotide Sequencing/methods , Respiratory Distress Syndrome/genetics , Gene Expression Profiling
17.
Int J Mol Sci ; 23(18)2022 Sep 09.
Article in English | MEDLINE | ID: covidwho-2039866

ABSTRACT

Medicinal plant microRNAs (miRNAs) are an endogenous class of small RNA central to the posttranscriptional regulation of gene expression. Biosynthetic research has shown that the mature miRNAs in medicinal plants can be produced from either the standard messenger RNA splicing mechanism or the pre-ribosomal RNA splicing process. The medicinal plant miRNA function is separated into two levels: (1) the cross-kingdom level, which is the regulation of disease-related genes in animal cells by oral intake, and (2) the intra-kingdom level, which is the participation of metabolism, development, and stress adaptation in homologous or heterologous plants. Increasing research continues to enrich the biosynthesis and function of medicinal plant miRNAs. In this review, peer-reviewed papers on medicinal plant miRNAs published on the Web of Science were discussed, covering a total of 78 species. The feasibility of the emerging role of medicinal plant miRNAs in regulating animal gene function was critically evaluated. Staged progress in intra-kingdom miRNA research has only been found in a few medicinal plants, which may be mainly inhibited by their long growth cycle, high demand for growth environment, immature genetic transformation, and difficult RNA extraction. The present review clarifies the research significance, opportunities, and challenges of medicinal plant miRNAs in drug development and agricultural production. The discussion of the latest results furthers the understanding of medicinal plant miRNAs and helps the rational design of the corresponding miRNA/target genes functional modules.


Subject(s)
MicroRNAs , Plants, Medicinal , Animals , Gene Expression Regulation, Plant , MicroRNAs/genetics , MicroRNAs/metabolism , Plants, Medicinal/genetics , Plants, Medicinal/metabolism , RNA, Messenger , RNA, Plant/genetics , RNA, Ribosomal
18.
Int J Mol Sci ; 23(18)2022 Sep 08.
Article in English | MEDLINE | ID: covidwho-2039865

ABSTRACT

Noncoding RNAs (ncRNAs), in the form of structural, catalytic or regulatory RNAs, have emerged to be critical effectors of many biological processes. With the advent of new technologies, we have begun to appreciate how intracellular and circulatory ncRNAs elegantly choreograph the regulation of gene expression and protein function(s) in the cell. Armed with this knowledge, the clinical utility of ncRNAs as biomarkers has been recently tested in a wide range of human diseases. In this review, we examine how critical factors govern the success of interrogating ncRNA biomarker expression in liquid biopsies and tissues to enhance our current clinical management of human diseases, particularly in the context of cancer. We also discuss strategies to overcome key challenges that preclude ncRNAs from becoming standard-of-care clinical biomarkers, including sample pre-analytics standardization, data cross-validation with closer attention to discordant findings, as well as correlation with clinical outcomes. Although harnessing multi-modal information from disease-associated noncoding RNome (ncRNome) in biofluids or in tissues using artificial intelligence or machine learning is at the nascent stage, it will undoubtedly fuel the community adoption of precision population health.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Artificial Intelligence , Biomarkers , Humans , MicroRNAs/genetics , Precision Medicine , RNA/genetics , RNA, Long Noncoding/genetics , RNA, Untranslated/genetics , RNA, Untranslated/metabolism
19.
Rom J Morphol Embryol ; 63(1): 55-59, 2022.
Article in English | MEDLINE | ID: covidwho-2026774

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic determined the use of different research methods and investigations in the management of this novel infectious disease. The impact and development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at cellular level is still a challenge and many directions of investigation have been opened, a complex topic that has been explored is the bidirectional interaction between host micro-ribonucleic acids (miRNAs) and viral miRNA. The main point of this study is to analyze the transcriptional modifications induced by the viral infection at ocular level, mediated by miRNAs. It is known that the ocular transmission is a route of infection, and it can cause multiple neuro-ophthalmological manifestations, such as optic nerve dysfunction, eye movement abnormalities, oscillopsia and intracranial hypertension. We have managed to identify more than six miRNAs specifically involved in eye disorders that are strongly dysregulated by the SARS-CoV-2. These miRNAs regulate different pathways, such as the nuclear factor-kappa B (NF-κB) pathway, the expression of complement factor H (CFH) gene, the expression of transforming growth factor-beta (TGF-ß), fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) genes. In the context of SARS-CoV-2 infection, many more molecular changes at ocular level need to be elucidated to better understanding the COVID-19.


Subject(s)
COVID-19 , MicroRNAs , Eye , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Pandemics , SARS-CoV-2
20.
Front Immunol ; 13: 985781, 2022.
Article in English | MEDLINE | ID: covidwho-2022758

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a severe pandemic that has posed an unprecedented challenge to public health worldwide. Hepatocellular carcinoma (HCC) is a common digestive system malignancy, with high aggressiveness and poor prognosis. HCC patients may be vulnerable to COVID-19. Since the anti-inflammatory, immunomodulatory and antiviral effects of vitamin D, we aimed to investigate the possible therapeutic effects and underlying action mechanisms of vitamin D in COVID-19 and HCC in this study. By using a range of bioinformatics and network pharmacology analyses, we identified many COVID-19/HCC target genes and analyzed their prognostic significance in HCC patients. Further, a risk score model with good predictive performance was developed to evaluate the prognosis of HCC patients with COVID-19 based on these target genes. Moreover, we identified seven possible pharmacological targets of vitamin D against COVID-19/HCC, including HMOX1, MB, TLR4, ALB, TTR, ACTA1 and RBP4. And we revealed the biological functions, signaling pathways and TF-miRNA coregulatory network of vitamin D in COVID-19/HCC. The enrichment analysis revealed that vitamin D could help in treating COVID-19/HCC effects through regulation of immune response, epithelial structure maintenance, regulation of chemokine and cytokine production involved in immune response and anti-inflammatory action. Finally, the molecular docking analyses were performed and showed that vitamin D possessed effective binding activity in COVID-19. Overall, we revealed the possible molecular mechanisms and pharmacological targets of vitamin D for treating COVID-19/HCC for the first time. But these findings need to be further validated in actual HCC patients with COVID-19 and need further investigation to confirm.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , COVID-19/complications , COVID-19/drug therapy , Vitamin D/therapeutic use , Molecular Docking Simulation , Toll-Like Receptor 4/metabolism , Vitamins/therapeutic use , MicroRNAs/genetics , Antiviral Agents/therapeutic use , Cytokines/metabolism , Retinol-Binding Proteins, Plasma
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