Epstein-Barr Virus Downregulates MicroRNA 203 through the Oncoprotein Latent Membrane Protein 1: a Contribution to Increased Tumor Incidence in Epithelial Cells

Yu, Haibo; Lu, Jianhong; Zuo, Lielian; Yan, Qijia; Yu, Zhengyuan; Li, Xiayu; Huang, Jin; Zhao, Lei; Tang, Hailin; Luo, Zhaohui; Liao, Qianjin; Zeng, Zhaoyang; Zhang, Junyi; Li, Guiyuan

doi:10.1128/jvi.05901-11

Cited by 66 publications

(75 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, we first measured the expression levels of a panel of miRNAs which have been shown to play important roles in certain cancer types including NSCLC [36][37][38][39][40][41]. Among these miRNAs, miR-29c-3p and miR-497-5p were up-regulated but miR-17-5p was down-regulated in A549-ER cells.…”

Section: Discussionmentioning

confidence: 99%

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

Zhang

Lin

Wang

et al. 2016

Journal of Drug Targeting

View full text Add to dashboard Cite

Non-small cell lung cancer (NSCLC) is the major cause of lung cancer-related deaths. Erlotinib is an effective drug for NSCLC patients, but its effect in advanced NSCLC is compromised because of the drug resistance. The mechanism of erlotinib resistance in NSCLC is largely unknown. In the current study, we found that erlotinib treatment down-regulated miR-17-5p level in A549 cells and miR-17-5p was lower in acquired erlotinib-resistant A549 cells (A549-ER) compared with erlotinib-sensitive A549 cells. Consistently, miR-17-5p was down-regulated in the tumor tissues and the plasma of erlotinib-resistant NSCLC patients in comparison to those who are sensitive to erlotinib. Moreover, miR-17-5p mimic increased the sensitivity of A549 and A549-ER to erlotinib. In contrast, miR-17-5p inhibitor decreased the cell death of A549 and A549-ER induced by erlotinib. In addition, we also demonstrated that miR-17-5p could inhibit the mRNA and protein levels of enhancer of zeste homolog (EZH) 1, a member of the EZH family that contributes to drug resistance in several types of cancer. The luciferase assay of 3 0 -untranslated region (UTR) demonstrates that EZH1 is a direct target of miR-17-5p and EZH1 RNAi recapitulates the effect of miR-17-5p overexpression on erlotinib resistance. Further, mutation in seed sequence of miR-17-5p could totally abolish the sensitization of A549-ER to erlotinib induced by miR-17-5p overexpression. Our results indicate that miR-17-5p down-regulation contributes to erlotinib resistance of NSCLC by modulating its target genes such as EZH1 and plasma miR-17-5p might be a potential biomarker of erlotinib response in NSCLC patients. ARTICLE HISTORY

show abstract

Section: Discussionmentioning

confidence: 99%

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

Zhang

Lin

Wang

et al. 2016

Journal of Drug Targeting

View full text Add to dashboard Cite

show abstract

“…An analysis of 41 NPC patients before and after radiotherapy showed that miR-BART7 and miR-BART13 were diminished after treatment, suggesting a potential use for them in terms of NPC serological diagnosis and prediction of treatment efficacy . The overexpression of EBV-miRBART10-3p in patients with NPC is significantly associated with poor disease-free and overall survival (Yan et al, 2012). These findings suggest that the effectiveness of current NPC treatments may be a result of the modulation of miRNA expression.…”

Section: Ebv-encoded and Ebv-dysregulated Mirnas Are Potential Biomarmentioning

confidence: 90%

“…LMP1 regulates the tumor microenvironment by inducing the NF-κB signaling pathway (Yu et al, 2012). As mentioned above, four EBV BARTmiRNAs co-target LMP1, potentially contributing to the modulation of the tumor microenvironment.…”

Section: Ebv Regulates the Inflammatory Tumor Microenvironment Via MImentioning

confidence: 96%

“…The miR-203 inhibited by EBV-LMP1 targets IL-8, which is a chemotaxis cytokine and immune response mediator (Yu et al, 2011;Yu et al, 2012;Qu et al, 2015). EBVinduced miR-155 and miR-146a are also important molecules in the regulation of the inflammatory reaction (Zhang et al, 2015a;Yang et al, 2016;Bitar et al, 2017).…”

Section: Ebv Regulates the Inflammatory Tumor Microenvironment Via MImentioning

confidence: 99%

“…A study revealed a significant correlation between miR-183 and the NPC N stages (Tang et al, 2012). In 16 patients with non-keratinizing undifferentiated NPC, the miR-146a expression level was significantly elevated and may be useful as an indicator of NPC development .…”

Section: Ebv-encoded and Ebv-dysregulated Mirnas Are Potential Biomarmentioning

confidence: 99%

See 2 more Smart Citations

An update: Epstein-Barr virus and immune evasion via microRNA regulation

Zuo

Yue

et al. 2017

Virol. Sin.

Self Cite

View full text Add to dashboard Cite

Epstein-Barr virus (EBV) is an oncogenic virus that ubiquitously establishes life-long persistence in humans.To ensure its survival and maintain its B cell transformation function, EBV has developed powerful strategies to evade host immune responses. Emerging evidence has shown that microRNAs (miRNAs) are powerful regulators of the maintenance of cellular homeostasis. In this review, we summarize current progress on how EBV utilizes miRNAs for immune evasion. EBV encodes miRNAs targeting both viral and host genes involved in the immune response. The miRNAs are found in two gene clusters, and recent studies have demonstrated that lack of these clusters increases the CD4 + and CD8 + T cell response of infected cells. These reports strongly indicate that EBV miRNAs are critical for immune evasion. In addition, EBV is able to dysregulate the expression of a variety of host miRNAs, which influence multiple immune-related molecules and signaling pathways. The transport via exosomes of EBV-regulated miRNAs and viral proteins contributes to the construction and modification of the inflammatory tumor microenvironment. During EBV immune evasion, viral proteins, immune cells, chemokines, pro-inflammatory cytokines, and pro-apoptosis molecules are involved. Our increasing knowledge of the role of miRNAs in immune evasion will improve the understanding of EBV persistence and help to develop new treatments for EBV-associated cancers and other diseases.

show abstract

Exosomal cyclophilin A as a novel noninvasive biomarker for Epstein‐Barr virus associated nasopharyngeal carcinoma

et al. 2019

Self Cite

View full text Add to dashboard Cite

Exosomes have emerged as novel vehicles for proteins and other contents in cancer progression. Cyclophilin A (CYPA) is a pivotal member of immunophilin family. Whether CYPA can be detected in sera of nasopharyngeal carcinoma (NPC) patients remains to be explored. Epstein‐Barr virus (EBV) is the first identified human tumor virus and is a causative agent of NPC. The antibody of EBV capsid antigen immunoglobulin A (EBV‐VCA‐IgA) is a known biomarker of NPC, with a proportion of no more than 70% being detected positively. Hence, novel biomarkers need to be discovered for early diagnosis, prognosis, and monitoring of EBV‐associated NPC. A total of 110 NPC and 36 normal control serum samples were collected. Exosomes from these samples were extracted. The mRNA and protein expression levels of the above samples were validated by reverse transcription –quantitative polymerase chain reaction, Western blotting, or enzyme‐linked immunosorbent assay (ELISA). Finally, the results demonstrated that both the serum and exosomal CYPA levels of NPC patients were significantly higher than that of normal cases. In addition, exosomal CYPA had a much higher level than that in the whole sera. The positive rate of EBV‐VCA‐IgA antibody was 68.2% in NPC sera, and noticeably, among the cases with EBV‐VCA‐IgA negative, 80% of them presented high levels of CYPA above the standard (cutoff value). In particular, CYPA in exosomes was uniformly with higher significance than that in whole sera. Combined analysis of CYPA protein and EBV‐VCA‐IgA antibody showed a greatly higher discriminatory ability in diagnosis of NPC. Moreover, exosomal CYPA level had a positive correlation with that of the EBV‐encoded latent membrane protein 1 (LMP1) in exosomes. EBV‐positive cancer cells secreted significantly higher levels of exosomal CYPA. This study established the utility of circulating exosomal CYPA as a potential noninvasive diagnostic biomarker for EBV‐associated NPC.

show abstract

Epstein-Barr Virus Downregulates MicroRNA 203 through the Oncoprotein Latent Membrane Protein 1: a Contribution to Increased Tumor Incidence in Epithelial Cells

Cited by 66 publications

References 54 publications

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

An update: Epstein-Barr virus and immune evasion via microRNA regulation

Exosomal cyclophilin A as a novel noninvasive biomarker for Epstein‐Barr virus associated nasopharyngeal carcinoma

Contact Info

Product

Resources

About