EBV-miR-BART8-3p induces epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma cells through activating NF-κB and Erk1/2 pathways

Lin, Cheng; Zong, Jingfeng; Lin, Wei; Wang, Minghui; Xu, Yujin; Zhou, Rui; Shen, Lin; Guo, Qiaojuan; Chen, Honglin; Ye, Yunbin; Zhang, Bin; Pan, Jianji

doi:10.1186/s13046-018-0953-6

Cited by 86 publications

(64 citation statements)

References 62 publications

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“…With the development of the research of BARTs, we began to explore the bridge between the treatment of resistance and metastasis. Studies have shown that 52 % of NPC demonstrated high level expression of EBV-miR-BART8-3p and could induce EMT, promoting the metastasis of cells [17], which was consistent with our results. In our previously reported study, we found that the EBV-encoded miRNA BART8-3p promoted radioresistance in nasopharyngeal carcinoma by regulating the ATM/ATR signaling pathway [18].…”

Section: Discussionsupporting

confidence: 93%

EBV Encoded miRNA BART8-3p Drives Radioresistance-Associated Metastasis in Nasopharyngeal Carcinoma

Zhou

Lin

Chen

et al. 2020

Preprint

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Background: Radiotherapy plays an important role in the treatment of nasopharyngeal carcinoma (NPC), however, 20 % of patients with NPC exhibit unusual radioresistance. Patients with radioresistance are at risk of recurrence, so it is imperative to explore the mechanism of resistance to radiotherapy. In the past, studies on the mechanism of radioresistance have been restricted to DNA damage and related cell cycle remodeling or apoptosis. So far, no studies have explored the relationship between radioresistance and metastasis. Methods: We analyzed the metastasis rate of patients with recurrent NPC and that of patients with primary NPC. Constructing an acquired radioresistant NPC cell line and detect their metastatic ability in vivo and in vitro. RNA-deep sequencing was performed to predict the targeted host genes of EBV-miR-BART8-3p. Western blotting, real-time PCR and immunochemistry were conducted to investigate the relationship of clinicopathologic features and EBV-miR-BART8-3p or PAG1. Results:Through the analysis of clinical samples, we observed that the metastasis rate of recurrent NPC was much higher than that of primary patients. In vitro and in vivo experiments showed that NPC cells with acquired radioresistance exhibited a stronger ability for invasion and metastasis. Mechanistically, we found that the Epstein–Barr virus (EBV)-encoded miRNA BART8-3p was increased in patients with NPC and its expression was positively correlated with adverse prognostic factors, such as radioresistance. Besides, miR-BART8-3p promoted the epithelial-mesenchymal transition (EMT), invasion, and metastasis of radioresistant NPC cells by targeting and inhibiting their PAG1 host gene. Conclusion: These results demonstrated a correlation between radioresistance and metastasis in NPC, which depended on the elevated levels of the EBV-encoded miRNA BART8-3p and the inhibition of the PAG1 host gene. These findings suggested a novel role for EBV-miR-BART8-3p and PAG1 in recurrence NPC and highlighted their potential value as prognostic indicators or therapeutic targets.

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Section: Discussionsupporting

confidence: 93%

EBV Encoded miRNA BART8-3p Drives Radioresistance-Associated Metastasis in Nasopharyngeal Carcinoma

Zhou

Lin

Chen

et al. 2020

Preprint

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“…showed that miR-BART7 promoted anchorage-independent growth. Additionally, several studies showed that BART miRNAs promoted cell migration [54,55]. Based on our KLF2 knockdown and overexpression data, the phenotype induced by miR-BART17-5p may be due to the decreased expression of KLF2.…”

Section: Discussionsupporting

confidence: 55%

Epstein-Barr Virus miR-BART17-5p Promotes Migration and Anchorage-Independent Growth by Targeting Kruppel-Like Factor 2 in Gastric Cancer

2020

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Epstein-Barr virus (EBV) infects more than 90% of the global population and is associated with a variety of tumors including nasopharyngeal carcinoma, Hodgkin lymphoma, natural killer/T lymphoma, and gastric carcinoma. In EBV-associated gastric cancer (EBVaGC), highly expressed EBV BamHI A rightward transcripts (BART) miRNAs may contribute to tumorigenesis with limited viral antigens. Despite previous studies on the targets of BART miRNAs, the functions of all 44 BART miRNAs have not been fully clarified. Here, we used RNA sequencing data from the Cancer Genome Atlas to find genes with decreased expression in EBVaGC. Furthermore, we used AGS cells infected with EBV to determine whether expression was reduced by BART miRNA. We showed that the expression of Kruppel-like factor 2 (KLF2) is lower in AGS-EBV cells than in the AGS control. Using bioinformatics analysis, four BART miRNAs were selected to check whether they suppress KLF2 expression. We found that only miR-BART17-5p directly down-regulated KLF2 and promoted gastric carcinoma cell migration and anchorage-independent growth. Our data suggest that KLF2 functions as a tumor suppressor in EBVaGC and that miR-BART17-5p may be a valuable target for effective EBVaGC treatment.

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“…The latter mechanism could represent the way by which human CMV induces endothelial dysfunction in CMV-mediated vascular diseases. Furthermore, ebv-miR-BART8-3p and ebv-miR-BART13 targets RNF38 (an E3 ubiquitin-protein ligase able to ubiquitinate p53) and NKIRAS2 (NF-kB Inhibitor) respectively [106][107][108], whereas ebv-miR-18-5p suppresses MAPK signaling by targeting MAP3K2, with consequent regulation of lytic viral replication [109]. Also, the NF-κB pathway is regulated by KSHV's miRNAs.…”

Section: Viral Efficient and Persistent Infection Regulationmentioning

confidence: 99%

“…Recently it has been shown that the overexpression of an EBV miRNA, ebv-miR-BART11, is involved in epithelial-mesenchymal transition (EMT) through the downregulation of FOXP1 [114], while ebv-miR-BART7-3p enhanced loss of epithelial markers and gain of mesenchymal features in neural progenitor cells (NPC) by targeting PTEN and thus affecting PI3K/Akt/GSK-3β signaling pathway [115]. Another study on NPC cells showed ebv-miR-BART8-3p plays a key role in EMT through the targeting RNF38 via the activation of NF-κB and Erk1/2 signaling pathways [107]. Furthermore, mTOR signaling, a key pathway for KSHV to induce transformation [116], is activated when KSHV miRNAs target mTOR inhibitory factor CASTOR1 [117].…”

Section: Cell Transformationmentioning

confidence: 99%

Non-Coding RNAs: Strategy for Viruses’ Offensive

Gallo

Bulati

Miceli

et al. 2020

ncRNA

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The awareness of viruses as a constant threat for human public health is a matter of fact and in this resides the need of understanding the mechanisms they use to trick the host. Viral non-coding RNAs are gaining much value and interest for the potential impact played in host gene regulation, acting as fine tuners of host cellular defense mechanisms. The implicit importance of v-ncRNAs resides first in the limited genomes size of viruses carrying only strictly necessary genomic sequences. The other crucial and appealing characteristic of v-ncRNAs is the non-immunogenicity, making them the perfect expedient to be used in the never-ending virus-host war. In this review, we wish to examine how DNA and RNA viruses have evolved a common strategy and which the crucial host pathways are targeted through v-ncRNAs in order to grant and facilitate their life cycle.

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EBV-miR-BART8-3p induces epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma cells through activating NF-κB and Erk1/2 pathways

Cited by 86 publications

References 62 publications

EBV Encoded miRNA BART8-3p Drives Radioresistance-Associated Metastasis in Nasopharyngeal Carcinoma

EBV Encoded miRNA BART8-3p Drives Radioresistance-Associated Metastasis in Nasopharyngeal Carcinoma

Epstein-Barr Virus miR-BART17-5p Promotes Migration and Anchorage-Independent Growth by Targeting Kruppel-Like Factor 2 in Gastric Cancer

Non-Coding RNAs: Strategy for Viruses’ Offensive

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