EBV encoded miRNA BART8-3p promotes radioresistance in nasopharyngeal carcinoma by regulating ATM/ATR signaling pathway

Zhou, Xiaohan; Zheng, Jialing; Tang, Ying; Lin, Yanling; Wang, Lingzhi; Li, Ye; Liu, Chengdong; Wu, De‐Hua; Cai, Longmei

doi:10.1042/bsr20190415

Cited by 30 publications

(21 citation statements)

References 28 publications

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Section: Non-coding Rna (Ncrna) and Ebv-associated Tumorsmentioning

confidence: 99%

“…Treatment with KU60019 or AZD6738 increases the radiosensitivity of NPC by suppressing the expression of p-ATM and p-ATR, indicating that EBV-miR-BART8-3p promoted radioresistance in NPC by modulating the activity of the ATM/ATR signaling pathway. 282 EBV-miR-BART13-3p. Vesicle-bound EBV-miR-BART13-3p in circulation distinguished NPC from other head and neck cancers and asymptomatic EBV-infections.…”

Section: Non-coding Rna (Ncrna) and Ebv-associated Tumorsmentioning

confidence: 99%

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Targeting the signaling in Epstein–Barr virus-associated diseases: mechanism, regulation, and clinical study

Cao

Xie

Shi

et al. 2021

Sig Transduct Target Ther

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Epstein–Barr virus-associated diseases are important global health concerns. As a group I carcinogen, EBV accounts for 1.5% of human malignances, including both epithelial- and lymphatic-originated tumors. Moreover, EBV plays an etiological and pathogenic role in a number of non-neoplastic diseases, and is even involved in multiple autoimmune diseases (SADs). In this review, we summarize and discuss some recent exciting discoveries in EBV research area, which including DNA methylation alterations, metabolic reprogramming, the changes of mitochondria and ubiquitin-proteasome system (UPS), oxidative stress and EBV lytic reactivation, variations in non-coding RNA (ncRNA), radiochemotherapy and immunotherapy. Understanding and learning from this advancement will further confirm the far-reaching and future value of therapeutic strategies in EBV-associated diseases.

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Section: Non-coding Rna (Ncrna) and Ebv-associated Tumorsmentioning

confidence: 99%

Section: Non-coding Rna (Ncrna) and Ebv-associated Tumorsmentioning

confidence: 99%

Targeting the signaling in Epstein–Barr virus-associated diseases: mechanism, regulation, and clinical study

Cao

Xie

Shi

et al. 2021

Sig Transduct Target Ther

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“…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]. In this study, we combined radioresistance with metastasis and found that radioresistant NPC cells were characterized by the overexpression of miR-BART8-3p , promoting PAG1-dependent EMT and metastasis.…”

Section: Discussionmentioning

confidence: 64%

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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“…There are also reports that miR-BART2-5p can be used as an early detection indicator for patients with nasopharyngeal carcinoma [16]. Experiments have shown that miR-BART8-3p can regulate ataxia telangiectasia mutations / ataxia telangiectasia mutations and Rad3 (ATM / ATR) The activity of related signaling pathways promotes NPC's radiation resistance [17]. MiR-BART15 is capable of targeting nucleotide-bound oligomerization domain-like receptor family pyridine domaincontaining 3 (NLRP3) with less in ammation to limit in ammation and promote EBV infection [18].…”

Section: Discussionmentioning

confidence: 99%

Plasma EBV miRNA Profiles Reveal Potential Biomarkers for Clinical Prognosis of Acquired Immunodeficiency Syndrome-related Lymphoma

Chen

Peng

Guo

et al. 2020

Preprint

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Background Acquired Immunodeficiency Syndrome-related lymphoma (ARL) is closely related to Epstein-Barr virus (EBV) infection. However, there are few studies on the occurrence and development of EBV miRNAs in ARL patients.Methods The plasma of 5 EBV-infected ARL patients and 8 EBV-infected HIV patients were screened for EBV miRNAs differentially expressed between the two groups through EBV microRNA quantification chip. The plasma of 35 EBV-infected ARL patients and 20 EBV-infected HIV patients was verified by qRT-PCR expanded samples. And we gave a further analysis of the correlation between differentially expressed EBV miRNAs and clinical prognosis indicators in ARL patients.Results 1. There were differential expressions of EBV miRNAs in the plasma of EBV-infected ARL patients and EBV-infected HIV patients. It was found that EBV-miR-BART2-5p,EBV-miR-BART8-3p,EBV-miR-BART15, EBV-miR-BART19-5p expression was significantly up-regulated and EBV-miR-BART9-5p expression was significantly down-regulated; 2. EBV microRNAs with significantly different expressions in the screening results were expanded and verified by qRT-PCR, and the differential expression was found to be consistent with the screening results; 3. The relative expression levels of EBV-miR-BART8-3p in plasma were positive correlated with the International Prognostic Index (IPI) score of Lymphoma(r = 0.37,P = 0.03),EBV-miR-BART19-5p was positive correlated with B symptoms (r = 0.42,P = 0.01) and EBV-miR-BART9-5p, was positive correlated with Eastern Cooperative Oncology Group (ECOG) scores (r = 0.35,P = 0.04).Conclusions The expression of EBV-miR-BART2-5p, EBV-miR-BART8-3p, EBV-miR-BART15,EBV-miR-BART19-5p,EBV-miR-BART9-5p in ARL patients were highly different; and EBV-miR-BART8-3p, EBV-miR-BART19-5p, EBV-miR-BART9-5p could be used as the biomarkers for the prognosis of ARL.

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EBV encoded miRNA BART8-3p promotes radioresistance in nasopharyngeal carcinoma by regulating ATM/ATR signaling pathway

Cited by 30 publications

References 28 publications

Targeting the signaling in Epstein–Barr virus-associated diseases: mechanism, regulation, and clinical study

Targeting the signaling in Epstein–Barr virus-associated diseases: mechanism, regulation, and clinical study

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

Plasma EBV miRNA Profiles Reveal Potential Biomarkers for Clinical Prognosis of Acquired Immunodeficiency Syndrome-related Lymphoma

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