In silico prediction of cellular gene targets of herpesvirus encoded microRNAs

Naqvi, Afsar Raza; Seal, Alexandra; Shango, Jennifer; Shukla, Deepak; Nares, Salvador

doi:10.1016/j.dib.2018.05.020

Cited by 7 publications

(5 citation statements)

References 8 publications

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“…In general, miRNAs and their direct target genes exhibit antagonistic expression patterns. We therefore selected all the downregulated genes from miR-H1 and miR-K12-3-3p datasets and scanned for potential v-miR binding sites [50].…”

Section: Resultsmentioning

confidence: 99%

“…These include cell replication, GPCR signaling, cell death, cell adhesion, etc. Moreover, employing in silico target prediction analysis, we identified hundreds of potential v-miR binding sites on the 3′UTRs of downregulated genes, even with stringent parameters [50; see Tables 1, 2 and supplementary data]. These genes are potentially regulated by v-miRs as our microarray data shows reduced mRNA levels and in silico analysis identifies single or in some cases, multiple v-miR binding sites suggesting that v-miR binding to host mRNA leads to transcript degradation.…”

Section: Discussionmentioning

confidence: 99%

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Herpesvirus-encoded microRNAs detected in human gingiva alter host cell transcriptome and regulate viral infection

Naqvi

Seal

Shango

et al. 2018

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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MicroRNAs (miRNAs) are small, non-coding RNAs of ~18-25 nucleotides that have gained extensive attention as critical regulators in complex gene networks including immune cell lineage commitment, differentiation, maturation, and maintenance of immune homeostasis and function. Many viruses encode miRNAs that directly downregulate the expression of factors of the innate immune system, which includes proteins involved in promoting apoptosis and recruitment. In this study, we examined the expression profiles of three previously identified viral miRNAs (v-miRs) from the human herpesvirus (HHV) family, HSV-1 (miR-H1), KSHV (miR-K12-3-3p), and HCMV (miR-US4) in healthy and diseased periodontal tissues and observed increased levels of v-miRs in diseased tissues. To understand the significance of this increase, we overexpressed v-miRs in human oral keratinocytes (HOK), a common target for various HHV, and analyzed the impact of miR-H1 and miR-K12-3-3p on the host transcriptome. More than 1300 genes were altered in HOK overexpressing miR-H1 and miR-K12-3-3p. Global pathway analysis of deregulated genes identified several key cellular pathways that may favor viral persistence. Using bioinformatic analysis, we predicted hundreds of potential v-miR binding sites on genes downregulated by miR-H1 and miR-K12-3-3p and validated three novel target v-miR sites suggesting widespread direct and indirect modulation of numerous host genes/pathways by a single v-miR. Finally, in vitro HSV-1 infection assays showed that miR-H1 can regulate viral entry and infection in human oral keratinocytes (HOK). Overall, our results demonstrate clinical and functional relevance of pathogenic viral molecules viz., v-miRs that regulate both host and viral functions and may contribute to the pathogenesis of inflammatory oral diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Herpesvirus-encoded microRNAs detected in human gingiva alter host cell transcriptome and regulate viral infection

Naqvi

Seal

Shango

et al. 2018

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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“…Additionally, similar to cellular miRNAs, viral miRNAs can also posttranscriptionally regulate numerous host genes. We recently showed that viral miRNAs can alter expression of both host mRNAs and miR-NAs in v-miR expressing oral keratinocytes and myeloid cells (macrophages) (Naqvi, Seal, Shango, Brambila, et al, 2018;Naqvi, Seal, Shango, Shukla, et al, 2018;Naqvi, Shango, Seal, Shukla, & Nares, 2018a). These widespread v-miR-mediated transcriptome changes can affect numerous cellular functions including immune responses, phagocytosis and cell migration.…”

Section: Studies From Various Groups Including Ours Have Demonstratedmentioning

confidence: 99%

Dysregulation of human miRNAs and increased prevalence of HHV miRNAs in obese periodontitis subjects

Naqvi

Brambila

Martínez

et al. 2019

J Clinic Periodontology

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Aim: To evaluate human and herpesvirus-encoded microRNA (miRNA) expression in healthy and diseased gingiva of obese and non-obese subjects and compare the impact of localized and systemic inflammation on human miRNA profiles. Material and methods: Healthy and inflamed gingival biopsies were collected from obese and non-obese subjects. Human and herpesvirus miRNA expression was quantified using quantitative PCR. Predicted targets of dysregulated miRNAs were identified using bioinformatics analysis, validated by dual luciferase assays and their expression assessed in healthy and diseased tissues. Results: Our results show differential expression of miRNAs in both diseased groups compared to healthy counterparts. MMP-16 is identified as a novel target of miRNAs altered in disease. Expression analysis of genes predicted as target of differentially expressed miRNAs show significant changes in disease compared with healthy tissues. Finally, quantitation of four herpesvirus derived viral miRNAs show that expression and prevalence of herpesvirus miRNAs in diseased gingiva of obese subjects. Conclusion: Our findings show that miRNA (both cellular and virus) expression are differentially responsive to local and systemic inflammation. Some of these miRNAs can modulate key cellular genes with direct consequences on inflammatory pathways suggesting their impact on oral tissue transcriptome and functions.

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“…To identify miR-142-3p gene targets with high confidence, we first selected downregulated genes. The 3′UTR of these genes were extracted using BioMart tool on Ensembl (http:// www.ensembl.org/biomart/martview/aa867419c3c6fd64f94af6d4a6549d3c) as previously described (31). Briefly, we selected Ensembl Genes 87 database and Human Genes dataset (GRCh38.p7).…”

Section: Mirna Target Prediction Of Differentially Downregulated Genesmentioning

confidence: 99%

Impaired cell migration and structural defects in myeloid cells overexpressing miR-30b and miR-142-3p

Valverde

Nares

Naqvi

2020

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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In silico prediction of cellular gene targets of herpesvirus encoded microRNAs

Cited by 7 publications

References 8 publications

Herpesvirus-encoded microRNAs detected in human gingiva alter host cell transcriptome and regulate viral infection

Herpesvirus-encoded microRNAs detected in human gingiva alter host cell transcriptome and regulate viral infection

Dysregulation of human miRNAs and increased prevalence of HHV miRNAs in obese periodontitis subjects

Impaired cell migration and structural defects in myeloid cells overexpressing miR-30b and miR-142-3p

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