HCMV miR-US22 down-regulation of EGR-1 regulates CD34+ hematopoietic progenitor cell proliferation and viral reactivation

Mikell, Iliyana; Crawford, Lindsey B.; Hancock, Meaghan H.; Mitchell, Joan S.; Buehler, Jason; Goodrum, Felicia; Nelson, Jay A.

doi:10.1101/645374

Cited by 17 publications

(26 citation statements)

References 59 publications

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“…Other cmv-miRs have functional roles during latency and reactivation [ 239 ]. While cmv-miR-US22 and cmv-miR-UL22A do not directly exert effects on the MIE enhancer/promoter, they influence HPC proliferation and differentiation [ 240 ], as well as myelosuppression and viral genomic maintenance [ 241 ], respectively.…”

Section: Microrna Regulation Of the Mie Locusmentioning

confidence: 99%

Regulation of the MIE Locus During HCMV Latency and Reactivation

Dooley

O’Connor

2020

Pathogens

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Human cytomegalovirus (HCMV) is a ubiquitous herpesviral pathogen that results in life-long infection. HCMV maintains a latent or quiescent infection in hematopoietic cells, which is broadly defined by transcriptional silencing and the absence of de novo virion production. However, upon cell differentiation coupled with immune dysfunction, the virus can reactivate, which leads to lytic replication in a variety of cell and tissue types. One of the mechanisms controlling the balance between latency and reactivation/lytic replication is the regulation of the major immediate-early (MIE) locus. This enhancer/promoter region is complex, and it is regulated by chromatinization and associated factors, as well as a variety of transcription factors. Herein, we discuss these factors and how they influence the MIE locus, which ultimately impacts the phase of HCMV infection.

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Section: Microrna Regulation Of the Mie Locusmentioning

confidence: 99%

Regulation of the MIE Locus During HCMV Latency and Reactivation

Dooley

O’Connor

2020

Pathogens

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“…It has been predicted that these miRNAs directly regulate the US22 transcript levels, and miR-US22-5p may target autophagy-related 5 (ATG5), a protein associated with autophagy and apoptosis, to modulate apoptosis [76]. Recently, EGR1 has been identified as a target of miR-US22 [41]. EGR1 regulates HCMV gene expression, and the downregulation of the transcription factor mediated by miR-US22 may contribute to the reactivation of HCMV [41,77].…”

Section: Mir-us22mentioning

confidence: 99%

“…Recently, EGR1 has been identified as a target of miR-US22 [41]. EGR1 regulates HCMV gene expression, and the downregulation of the transcription factor mediated by miR-US22 may contribute to the reactivation of HCMV [41,77].…”

Section: Mir-us22mentioning

confidence: 99%

MicroRNAs expressed by human cytomegalovirus

Zhang

Liu

2020

Virol J

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Background: MicroRNAs (miRNAs) are small non-coding RNAs about 22 nucleotides in length, which play an important role in gene regulation of both eukaryotes and viruses. They can promote RNA cleavage and repress translation via base-pairing with complementary sequences within mRNA molecules. Main body: Human cytomegalovirus (HCMV) encodes a large number of miRNAs that regulate transcriptions of both host cells and themselves to favor viral infection and inhibit the host's immune response. To date,~26 mature HCMV miRNAs have been identified. Nevertheless, their roles in viral infection are ambiguous, and the mechanisms have not been fully revealed. Therefore, we discuss the methods used in HCMV miRNA research and summarize the important roles of HCMV miRNAs and their potential mechanisms in infection. Conclusions: To study the miRNAs encoded by viruses and their roles in viral replication, expression, and infection will not only contribute to the planning of effective antiviral therapies, but also provide new molecular targets for the development of antiviral drugs.

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“…MiRNAs are classes of short RNA molecules with 19 to 25 nucleotides, which regarded as one of the regulators of gene expression and silenced target genes in post-transcriptional levels. Growing evidences suggested that miRNAs participate in biological process, for instance, DNA damage response, cell proliferation, cell apoptosis [13][14][15]. With further understanding of biological process, a new regulatory mechanism named competing endogenous RNA (ceRNA) was proposed, which provides a better insight into tumorigenesis [16].…”

Section: Ivyspringmentioning

confidence: 99%

Comprehensive analysis of TPX2-related ceRNA network as prognostic biomarkers in lung adenocarcinoma

Chen¹,

Zhang²,

Li³

et al. 2020

Int. J. Med. Sci.

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Background and aim: Competing endogenous RNA (ceRNA) is believed to play vital roles in tumorigenesis. The goal of this study was to screen prognostic biomarkers in lung adenocarcinoma (LUAD). Methods: Common differentially expressed genes (DEGs) were collected from Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas databases (TCGA) using GEO2R and "limma" package in R, respectively. Overlapping DEGs were conducted using enrichment of functions and protein-protein interaction (PPI) network to discover significant candidate genes. By using a comprehensive analysis, we constructed an mRNA mediated ceRNA network. Survival rates were used Kaplan-Meier analysis. Statistical analysis was used to further identify the prognosis of studied genes. Results: Integrated analysis of GSE32863 and TCGA databases, a total of 886 overlapping DEGs, including 279 up-regulated and 607 down-regulated genes were identified. Considering the highest term of candidate genes in PPI, we identified TPX2, which was enriched in cell division signaling pathway. Besides, 35 differentially expressed miRNAs (DEmiRNAs) were predicted to target TPX2 and only 7 DEmiRNAs were identified to be prognostic biomarkers in LUAD. Then, 30 differentially expressed lncRNAs (DElncRNAs) were predicted to bind these 7 DEmiRNAs. Finally, we found that 7 DElncRNAs were correlated with the overall survival (all p <0.05). Furthermore, we identified elevated TPX2 was strongly correlated with the worse survival rate among 458 samples. Univariate and multivariate cox analysis showed TPX2 may act as an independent factor for prognosis in LUAD (p <0.05). Then pathway enrichment results suggested that TPX2 may facilitate tumorigenesis by participating in several cancer-related signaling pathways in LUAD, especially in Notch signal pathway. Conclusions: TPX2-related lncRNAs and miRNAs are related to the survival of LUAD. 7 lncRNAs, 7 miRNAs and TPX2 may serve as prognostic biomarkers in LUAD.

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HCMV miR-US22 down-regulation of EGR-1 regulates CD34+ hematopoietic progenitor cell proliferation and viral reactivation

Cited by 17 publications

References 59 publications

Regulation of the MIE Locus During HCMV Latency and Reactivation

Regulation of the MIE Locus During HCMV Latency and Reactivation

MicroRNAs expressed by human cytomegalovirus

Comprehensive analysis of TPX2-related ceRNA network as prognostic biomarkers in lung adenocarcinoma

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