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Journal of Virology May 2024The host-virus interactome is increasingly recognized as an important research field to discover new therapeutic targets to treat influenza. Multiple pooled genome-wide... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The host-virus interactome is increasingly recognized as an important research field to discover new therapeutic targets to treat influenza. Multiple pooled genome-wide CRISPR-Cas screens have been reported to identify new pro- and antiviral host factors of the influenza A virus. However, at present, a comprehensive summary of the results is lacking. We performed a systematic review of all reported CRISPR studies in this field in combination with a meta-analysis using the algorithm of meta-analysis by information content (MAIC). Two ranked gene lists were generated based on evidence in 15 proviral and 4 antiviral screens. Enriched pathways in the proviral MAIC results were compared to those of a prior array-based RNA interference (RNAi) meta-analysis. The top 50 proviral MAIC list contained genes whose role requires further elucidation, such as the endosomal ion channel and the kinase . Moreover, MAIC indicated that , a component of the transcription export complex, has antiviral properties, whereas former knockdown experiments attributed a proviral role to this host factor. CRISPR-Cas-pooled screens displayed a bias toward early-replication events, whereas the prior RNAi meta-analysis covered early and late-stage events. RNAi screens led to the identification of a larger fraction of essential genes than CRISPR screens. In summary, the MAIC algorithm points toward the importance of several less well-known pathways in host-influenza virus interactions that merit further investigation. The results from this meta-analysis of CRISPR screens in influenza A virus infection may help guide future research efforts to develop host-directed anti-influenza drugs.
IMPORTANCE
Viruses rely on host factors for their replication, whereas the host cell has evolved virus restriction factors. These factors represent potential targets for host-oriented antiviral therapies. Multiple pooled genome-wide CRISPR-Cas screens have been reported to identify pro- and antiviral host factors in the context of influenza virus infection. We performed a comprehensive analysis of the outcome of these screens based on the publicly available gene lists, using the recently developed algorithm meta-analysis by information content (MAIC). MAIC allows the systematic integration of ranked and unranked gene lists into a final ranked gene list. This approach highlighted poorly characterized host factors and pathways with evidence from multiple screens, such as the vesicle docking and lipid metabolism pathways, which merit further exploration.
Topics: Humans; Influenza A virus; CRISPR-Cas Systems; Influenza, Human; Host-Pathogen Interactions; Virus Replication; Clustered Regularly Interspaced Short Palindromic Repeats; RNA Interference
PubMed: 38567969
DOI: 10.1128/jvi.01857-23 -
Epigenomics Oct 2021A systematic review was conducted to identify the association of miRNA expression with HIV pathogenesis, progression and treatment. A search of articles was conducted... (Meta-Analysis)
Meta-Analysis
A systematic review was conducted to identify the association of miRNA expression with HIV pathogenesis, progression and treatment. A search of articles was conducted in MEDLINE, Cochrane Central Register of Controlled Trials and Global Health. 35 articles were included. Due to the heterogeneity of HIV phenotypes, a harmonization based on key progression parameters was proposed. The hsa-miR-29 family, hsa-miR-146b-5p and hsa-miR-150-5p, are the most frequently differentially expressed in HIV. Direct comparison of studies was not possible due to heterogeneity in biological samples and miRNA analysis techniques. This is the first attempt to systematically identify miRNA's different expression in well-defined patient phenotypes and could represent a helpful way to increase general knowledge in this field.
Topics: Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Computational Biology; Disease Management; Disease Susceptibility; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; HIV Infections; Host-Pathogen Interactions; Humans; MicroRNAs; Prognosis; RNA Interference; Transcriptome; Treatment Outcome; Viral Load
PubMed: 34693727
DOI: 10.2217/epi-2021-0237 -
Briefings in Functional Genomics Apr 2023Neurodegenerative diseases (NDDs) are on the rise in the world. Therefore, it is a critical issue to reveal the precise pathophysiological mechanisms and novel...
Neurodegenerative diseases (NDDs) are on the rise in the world. Therefore, it is a critical issue to reveal the precise pathophysiological mechanisms and novel therapeutic strategies to deal with such conditions. Passing through different mechanisms, non-coding RNAs (ncRNAs) play a pivotal role in NDDs through various mechanisms, by changing the expression of some genes, interference with protein translation and alterations in some signaling pathways. It urges the need to introduce novel strategies and therapeutic agents with multi-targeting potentials. Phytochemicals are hopeful antioxidants and anti-inflammatory agents with promising modulatory roles on dysregulated signaling pathways and protein translation during NDDs. In this study, the role of ncRNAs (e.g. lncRNAs, miRNA, siRNAs and piRNAs) was highlighted in NDDs. This study also aimed to investigate the role of phytochemicals (phenolic compounds, alkaloids, terpenoids and sulfur compounds) in the modulation of ncRNAs during NDDs such as Alzheimer's disease, Parkinson's disease, epilepsy, depression and amyotrophic lateral sclerosis.
Topics: Humans; Neurodegenerative Diseases; Alzheimer Disease; Parkinson Disease; RNA, Untranslated; Phytochemicals
PubMed: 36722043
DOI: 10.1093/bfgp/elac055 -
Critical Reviews in Oncology/hematology Sep 2019Long non-coding RNAs (lncRNAs), are over 200 nucleotides in length, and they rarely act as templates for protein synthesis. Mounting studies have shown that lncRNAs play...
Long non-coding RNAs (lncRNAs), are over 200 nucleotides in length, and they rarely act as templates for protein synthesis. Mounting studies have shown that lncRNAs play a crucial regulatory role in various processes that sustain life, such as epigenetic regulation, cell cycle control, splicing, and post-transcriptional regulation. LncRNAs were aberrantly expressed in most hematological malignancies including lymphoma, participating in tumor suppression or promoting oncogenesis and modulating key genes in different pathways. The specific expression patterns of lncRNAs in lymphoma make them good candidates to be used as diagnostic biomarkers or as therapeutic targets. LncRNAs can be targeted by multiple approaches including nucleic acid therapeutics, CRISPR/Cas genome editing techniques, small molecule inhibitors, and gene therapy. Efforts are made to develop therapeutic strategies aimed at targeting lncRNAs, but there are still some avenues to be covered before they can be applied to the clinical treatment of lymphoma.
Topics: Biomarkers, Pharmacological; Biomarkers, Tumor; Cell Transformation, Neoplastic; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; Lymphoma; Molecular Targeted Therapy; RNA Interference; RNA, Long Noncoding
PubMed: 31202125
DOI: 10.1016/j.critrevonc.2019.05.007 -
International Journal of Molecular... Aug 2019MiRNAs have been shown to play a crucial role among lung cancer, pulmonary fibrosis, tuberculosis (TBC) infection, and bronchial hypersensitivity, thus including chronic... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
MiRNAs have been shown to play a crucial role among lung cancer, pulmonary fibrosis, tuberculosis (TBC) infection, and bronchial hypersensitivity, thus including chronic obstructive pulmonary disease (COPD) and asthma. The oncogenic effect of several miRNAs has been recently ruled out. In order to act on miRNAs turnover, antagomiRs have been developed.
MATERIALS AND METHODS
The systematic review was conducted under the PRISMA guidelines (registration number is: CRD42019134173). The PubMed database was searched between 1 January 2000 and 30 April 2019 under the following search strategy: (((antagomiR) OR (mirna antagonists) OR (mirna antagonist)) AND ((lung[MeSH Terms]) OR ("lung diseases"[MeSH Terms]))). We included original articles, published in English, whereas exclusion criteria included reviews, meta-analyses, single case reports, and studies published in a language other than English.
RESULTS AND CONCLUSIONS
A total of 68 articles matching the inclusion criteria were retrieved. Overall, the use of antagomiR was seen to be efficient in downregulating the specific miRNA they are conceived for. The usefulness of antagomiRs was demonstrated in humans, animal models, and cell lines. To our best knowledge, this is the first article to encompass evidence regarding miRNAs and their respective antagomiRs in the lung, in order to provide readers a comprehensive review upon major lung disorders.
Topics: Animals; Antagomirs; Biomarkers; Cell Line; Cells, Cultured; Gene Expression Regulation; Humans; Lung Diseases; MicroRNAs; Models, Animal; RNA Interference
PubMed: 31412612
DOI: 10.3390/ijms20163938