Epstein-Barr virus miR-BART1-3p suppresses apoptosis and promotes migration of gastric carcinoma cells by targeting DAB2

Min, Kyoungmi; Kim, Jun Yeob; Lee, Suk Kyeong

doi:10.7150/ijbs.36595

Cited by 23 publications

(18 citation statements)

References 43 publications

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“…These findings suggest that miR-BART1-3p increases resistance to DNA-damage-induced apoptosis by affecting E2F3. Previously, we showed that miR-BART1-3p can inhibit cell apoptosis by acting on disabled homolog 2 (DAB2) in addition to E2F3 [11], suggesting that miRNAs fine tune cell function by targeting multiple genes with overlapping functions.…”

Section: Discussionmentioning

confidence: 99%

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Epstein-Barr Virus miR-BART1-3p Regulates the miR-17-92 Cluster by Targeting E2F3

Park

Kim

Choi

et al. 2021

IJMS

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Epstein-Barr virus (EBV) is associated with several tumors and generates BamHI A rightward transcript (BART) microRNAs (miRNAs) from BART transcript introns. These BART miRNAs are expressed at higher levels in EBV-associated epithelial malignancies than in EBV-infected B lymphomas. To test the effects of EBV miRNA on the cell cycle and cell growth, we transfected miR-BART1-3p, a highly expressed EBV-associated miRNA, into gastric carcinoma cells. We found that miR-BART1-3p induced G0/G1 arrest and suppressed cell growth in gastric carcinoma cells. As our microarray analyses showed that E2F3, a cell cycle regulator, was inhibited by EBV infection, we hypothesized that miR-BART1-3p regulates E2F3. Luciferase assays revealed that miR-BART1-3p directly targeted the 3′-UTR of E2F3 mRNA. Both E2F3 mRNA and encoded protein levels were reduced following miR-BART1-3p transfection. In contrast, E2F3 expression in AGS-EBV cells transfected with a miR-BART1-3p inhibitor was enhanced. As E2F3 has been shown to regulate the expression of highly conserved miR-17-92 clusters in vertebrates, we examined whether this expression is affected by miR-BART1-3p, which can downregulate E2F3. The expression of E2F3, miR-17-92a-1 cluster host gene (MIR17HG), and miR-17-92 cluster miRNAs was significantly reduced in EBV-associated gastric carcinoma (EBVaGC) patients compared with EBV-negative gastric carcinoma (EBVnGC) patients. Further, miR-BART1-3p as well as the siRNA specific to E2F3 inhibited the expression of the miR-17-92 cluster, while inhibition of miR-BART1-3p enhanced the expression of the miR-17-92 cluster in cultured GC cells. Our results suggest a possible role of miR-BART1-3p in cell cycle regulation and in regulation of the miR-17-92 cluster through E2F3 suppression.

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Section: Discussionmentioning

confidence: 99%

“…The EBV miRNA miR-BART1-3p is one of the most highly expressed miRNAs in EBV-associated carcinomas such as GC and NPC [9,10]. Recently, we showed that transfection of a miR-BART1-3p mimic into gastric carcinoma cells caused the cells to accumulate at the G0/G1 phase and suppressed cell apoptosis by suppressing DAB2 [11].…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus miR-BART1-3p Regulates the miR-17-92 Cluster by Targeting E2F3

Park

Kim

Choi

et al. 2021

IJMS

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“…Dab2 is involved in suppression of apoptosis by Epstein-Barr virus (EBV) (40). Two nodes, mitochondrial antiviral signaling protein (MAVS) and DExD/H-Box Helicase 58 (DDX58) were reported as antiviral proteins (41,42).…”

Section: Discussionmentioning

confidence: 99%

Companion diagnostic for the chloroquine use in the treatment of COVID-19: systems biology report of candidate markers.

Souchelnytskyi

2020

Preprint

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BACKGROUND Chloroquine is used for the treatment of COVID-19 patients. However, efficacy of the chloroquine has been under discussion. Variability of clinical outputs of the drug application requires implementation of a companion diagnostic that would allow monitoring responsiveness to chloroquine. The first line of such markers would be markers already used in clinics. Analysis of reported mechanisms of COVID-19 and chloroquine may lead to such markers. METHODS Systemic analysis of molecular mechanisms and markers engaged by chloroquine and COVID-19 virus was performed. The networks of regulatory mechanisms were explored for an intersection and relevance to clinical markers. RESULTS Reported here systemic analysis describes the intersection of molecular mechanisms of chloroquine and processes engaged by COVID-19. 266 nodes provide insight into the mechanisms of chloroquine impact on the infection and represent a pool of companion diagnostic markers. As an example, an intersection with the markers of heart arrhythmia retrieved 19 nodes. Thirteen of them were reported in human plasma: levels of albumin, amyloid precursor protein, and endoglin correlate with adverse cardiac effects. CONCLUSIONS Reported nodes are the candidate markers for companion diagnostic of the chloroquine application to COVID-19 patients. Some of these markers are already used in the clinic and their interpretation may contribute to monitoring for adverse effects of chloroquine.

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Section: Discussionmentioning

confidence: 99%

Chloroquine use in the Treatment of COVID-19: Systems Biology Report of Common Targets of SARS-CoV-2 and Chloroquine.

Souchelnytskyi

2020

Preprint

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BACKGROUND: Chloroquine use for treatment of COVID-19 patients has been under discussion and recommendations have been shifting from positive to caution or non-conclusive. Variability of clinical outputs requires understanding of mechanisms of the differences. Implementation of a companion diagnostic would allow selecting patients who may benefit from the drug. The first line would be markers already used in clinics. Systems biology opens for an opportunity to identify targets common for chloroquine and SARS-CoV-2. These common targets would be candidates for the companion diagnostic.METHODS: Systemic analysis of molecular mechanisms and markers engaged by chloroquine and SARS-CoV-2 virus was performed. The networks of regulatory mechanisms were explored for an intersection and relevance to clinical markers.RESULTS: Reported here systemic analysis describes the intersection of molecular mechanisms of chloroquine and processes engaged by COVID-19. 266 nodes provide insight into the mechanisms of chloroquine impact on the infection and represent a pool of companion diagnostic markers. As an example, an intersection with the markers of heart arrhythmia retrieved 19 nodes. Thirteen of them were reported in human plasma: levels of albumin, amyloid precursor protein, and endoglin correlate with adverse cardiac effects. CONCLUSIONS: Reported intersection nodes of SARS-CoV-2 and chloroquine are the candidate markers for companion diagnostic of the chloroquine application. Some of these markers are already used in the clinic and their interpretation may contribute to monitoring for adverse effects of chloroquine.

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Epstein-Barr virus miR-BART1-3p suppresses apoptosis and promotes migration of gastric carcinoma cells by targeting DAB2

Cited by 23 publications

References 43 publications

Epstein-Barr Virus miR-BART1-3p Regulates the miR-17-92 Cluster by Targeting E2F3

Epstein-Barr Virus miR-BART1-3p Regulates the miR-17-92 Cluster by Targeting E2F3

Companion diagnostic for the chloroquine use in the treatment of COVID-19: systems biology report of candidate markers.

Chloroquine use in the Treatment of COVID-19: Systems Biology Report of Common Targets of SARS-CoV-2 and Chloroquine.

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