Viral infection linked to m6A alterations in host mRNAs

Barranco, Caroline

doi:10.1038/s41580-019-0202-7

Cited by 11 publications

(10 citation statements)

References 2 publications

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“…The “immune system” ( P value: 9.57 × 10 −18 ) ( 12 ) was identified for the immune response (IR). The “metabolism of RNA” ( P value: 5.37 × 10 −45 ) ( 12 , 13 ) and “cell cycle” ( P value: 1.73 × 10 −16 ) ( 14 ) were found for viral replication. The key proteins belonging to these three pathways were assigned to the three subgroups (purple, metabolism of RNA; red, cell cycle; and light blue, immune system) under the hidden layer in Fig.…”

Section: Resultsmentioning

confidence: 99%

Identification of SARS-CoV-2–induced pathways reveals drug repurposing strategies

et al. 2021

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The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates the rapid development of new therapies against coronavirus disease 2019 (COVID-19) infection. Here, we present the identification of 200 approved drugs, appropriate for repurposing against COVID-19. We constructed a SARS-CoV-2–induced protein network, based on disease signatures defined by COVID-19 multiomics datasets, and cross-examined these pathways against approved drugs. This analysis identified 200 drugs predicted to target SARS-CoV-2–induced pathways, 40 of which are already in COVID-19 clinical trials, testifying to the validity of the approach. Using artificial neural network analysis, we classified these 200 drugs into nine distinct pathways, within two overarching mechanisms of action (MoAs): viral replication (126) and immune response (74). Two drugs (proguanil and sulfasalazine) implicated in viral replication were shown to inhibit replication in cell assays. This unbiased and validated analysis opens new avenues for the rapid repurposing of approved drugs into clinical trials.

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Section: Resultsmentioning

confidence: 99%

Identification of SARS-CoV-2–induced pathways reveals drug repurposing strategies

et al. 2021

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“…N6-methyladenosine (m 6 A) modification is the most abundant posttranscriptional internal mRNA modification in eukaryotes [ 13 , 14 ]. This modification is reversible, and its biological effects are mostly mediated through ‘writer’, ‘eraser’ and ‘reader’ proteins [ 13 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

YTHDC1-mediated augmentation of miR-30d in repressing pancreatic tumorigenesis via attenuation of RUNX1-induced transcriptional activation of Warburg effect

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers. It thrives in a malnourished environment; however, little is known about the mechanisms by which PDAC cells actively promote aerobic glycolysis to maintain their metabolic needs. Gene Expression Omnibus (GEO) was used to identify differentially expressed miRNAs. The expression pattern of miR-30d in normal and PDAC tissues was studied by in situ hybridization. The role of miR-30d/RUNX1 in vitro and in vivo was evaluated by CCK8 assay and clonogenic formation as well as transwell experiment, subcutaneous xenograft model and liver metastasis model, respectively. Glucose uptake, ATP and lactate production were tested to study the regulatory effect of miR-30d/RUNX1 on aerobic glycolysis in PDAC cells. Quantitative real-time PCR, western blot, Chip assay, promoter luciferase activity, RIP, MeRIP, and RNA stability assay were used to explore the molecular mechanism of YTHDC1/miR-30d/RUNX1 in PDAC. Here, we discover that miR-30d expression was remarkably decreased in PDAC tissues and associated with good prognosis, contributed to the suppression of tumor growth and metastasis, and attenuation of Warburg effect. Mechanistically, the m6A reader YTHDC1 facilitated the biogenesis of mature miR-30d via m6A-mediated regulation of mRNA stability. Then, miR-30d inhibited aerobic glycolysis through regulating SLC2A1 and HK1 expression by directly targeting the transcription factor RUNX1, which bound to the promoters of the SLC2A1 and HK1 genes. Moreover, miR-30d was clinically inversely correlated with RUNX1, SLC2A1 and HK1, which function as adverse prognosis factors for overall survival in PDAC tissues. Overall, we demonstrated that miR-30d is a functional and clinical tumor-suppressive gene in PDAC. Our findings further uncover that miR-30d is a novel target for YTHDC1 through m6A modification, and miR-30d represses pancreatic tumorigenesis via suppressing aerobic glycolysis.

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“…4 A, B). The top enriched GO BPs of key proteins identified by eigenvector centrality are viral replication related terms such as mRNA metabolic processes, viral transcription, and viral gene expression [25] , [26] ( Fig. 4 C).…”

Section: Resultsmentioning

confidence: 99%

“…At the highest hierarchical level in the Reactome pathway database, ‘Immune System’ (SARS FDR-BH: 2.05e-23; COVID-19 FDR-BH: 4.96e-19) [25] was identified for the immune response related biological pathway. The ‘Metabolism of RNA’ (SARS FDR-BH: 3.11e-37; COVID-19 FDR-BH: 3.53e-58) [25] , [26] ‘Metabolism of Protein’ (SARS FDR-BH: 3.45e-15; COVID-19 FDR-BH: 4.56e-42) [30] and ‘Cell Cycle’ (SARS FDR-BH: 6.66e-20; COVID-19, FDR-BH: 1.59e-15) [31] were identified for viral replication related biological pathways. The key proteins belonging to these four pathways were assigned to the four band groups under the ‘Hidden Layer’ in Fig.…”

Section: Resultsmentioning

confidence: 99%

Identification of potential pan-coronavirus therapies using a computational drug repurposing platform

Hwang

Han

2022

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Viral infection linked to m6A alterations in host mRNAs

Cited by 11 publications

References 2 publications

Identification of SARS-CoV-2–induced pathways reveals drug repurposing strategies

Identification of SARS-CoV-2–induced pathways reveals drug repurposing strategies

YTHDC1-mediated augmentation of miR-30d in repressing pancreatic tumorigenesis via attenuation of RUNX1-induced transcriptional activation of Warburg effect

Identification of potential pan-coronavirus therapies using a computational drug repurposing platform

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