Comprehensive profiling of Epstein-Barr virus-encoded miRNA species associated with specific latency types in tumor cells

Yang, Hong; Huang, Tie Jun; Yang, Chang Fu; Li, Peng; Liu, Ran Yi; Yang, Guang; Chu, Qiao Qiao; Huang, Junting; Liu, Na; Hong, Huixiao; Zhu, Zhen; Qian, Chao Nan; Huang, Bi

doi:10.1186/1743-422x-10-314

Cited by 46 publications

(37 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3D). Unlike typical pre-miRNAs, pre-miR-BART-18 has been reported to give rise to both abundant 5′ (5p) and 3′ derivate (3p) miRNAs, depending on cellular context (39,42,43). We confirmed that expression of pre-miR-BART-18 gives rise to approximately equally abundant 5p and 3p derivatives in HEK293T cells (Fig.…”

Section: Significancesupporting

confidence: 77%

RETRACTED: Pan-viral-microRNA screening identifies interferon inhibition as a common function of diverse viruses

Cox

McClure

Goga

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Diverse viruses encode regulatory RNAs called microRNAs (miRNAs). Despite much progress, the functions of the majority of viral miRNAs remain unknown. Most previous studies have used biochemical methods to uncover targets of viral miRNAs, but it is unclear what fraction of these targets is functionally important. Here, we apply an alternative strategy based on the premise that assorted viral miRNAs will share functionality. Screening a library of >70 human viral miRNAs showed that three unrelated miRNAs from distantly related herpesviruses significantly inhibited IFN signaling. Strikingly, each of these miRNAs directly reduced expression of the cyclic AMP-responsive element-binding protein (CBP), which as part of the p300-CBP complex, mediates IFN signaling. We show that both 5′ and 3′ derivatives from Epstein–Barr virus (EBV) encoded miR-BART-18 precursor miRNA (pre-miRNA) and the orthologous pre-miRNA from Rhesus lymphocryptovirus contribute to reducing IFN signaling. Thus, through both convergent and divergent evolutionary mechanisms, varied herpesviral miRNAs share the ability to decrease IFN signaling. Restoring miR-BART-18 to cells infected with an EBV miRNA mutant conveyed a cellular growth advantage upon IFN treatment, and relevant miRNAs from other herpesviruses were able to complement this activity. Blocking miR-BART-18 function in an EBV+ tumor cell line renders cells more susceptible to IFN-mediated effects. These findings provide a mechanism that can at least partially explain the resistance of some EBV-associated tumors to IFN therapy. Our work suggests that similar pan-viral-miRNA functional-based screening strategies are warranted for determining relevant activities of other viral miRNAs.

show abstract

Section: Significancesupporting

confidence: 77%

RETRACTED: Pan-viral-microRNA screening identifies interferon inhibition as a common function of diverse viruses

Cox

McClure

Goga

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Silencing of endogenous EBV-miR-BART7-3p attenuates the EMT and cell migration in EBV-positive NPC cells EBV-miR-BARTs were preferentially expressed in EBV-infected epithelial cells, 25,39,40 so we replicated our experiments in the EBV-positive NPC cell line to validate our findings. NPC EBVpositive cell lines (C666-1-EBV, HONE1-EBV and HK1-EBV) were initially confirmed to express EBV-miR-BART7-3p at a similar level to CNE1-BART7-3P cells, 5-8F-BART7-3p cells and NPC tissues (Supplementary Figure S6a).…”

Section: Resultsmentioning

confidence: 53%

“…This virus expresses more than 40 mature miRNAs in latently infected cells. Of them, some miRNAs encoded by BamH I-A rightward transcripts (BARTs) of EBV are disclosed to be highly expressed in some cancers such as gastric cancer, 23 lymphomas 24 and NPC, [25][26][27] contributing to viral latency, [28][29][30] host cell survival, 30,31 immune escape, 32 cell proliferation, 33 cell apoptosis 31,34 and cancer metabolism. 35 However, there have been few reports of the relationship between viral miRNAs and EMT in cancer to date.…”

Section: Introductionmentioning

confidence: 99%

EBV-miR-BART7-3p promotes the EMT and metastasis of nasopharyngeal carcinoma cells by suppressing the tumor suppressor PTEN

et al. 2014

View full text Add to dashboard Cite

The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.

show abstract

“…In addition to hosts, a number of viruses, including WNV (3), bovine leukemia virus (23), Epstein-Barr virus (24), herpesviruses (25), and others (26), encode miRNAs, which regulate host and viral genes to enhance viral replication. Viruses can also recruit cellular miRNAs to facilitate their replication.…”

mentioning

confidence: 99%

Expression of Mosquito MicroRNA Aae-miR-2940-5p Is Downregulated in Response to West Nile Virus Infection To Restrict Viral Replication

Slonchak

Hussain

Torres

et al. 2014

J Virol

View full text Add to dashboard Cite

West Nile virus (WNV) is an enveloped virus with a single-stranded positive-sense RNA genome from the Flaviviridae family. WNV is spread by mosquitoes and able to infect humans, causing encephalitis and meningitis that can be fatal; it therefore presents a significant risk for human health. In insects, innate response to RNA virus infection mostly relies on RNA interference and JAK/SAT pathways; however, some evidence indicates that it can also involve microRNAs (miRNAs). miRNAs are small noncoding RNAs that regulate gene expression at posttranscriptional level and play an important role in a number of processes, including immunity and antiviral response. In this study, we focus on the miRNA-mediated response to WNV in mosquito cells. We demonstrate that in response to WNV infection the expression of a mosquito-specific miRNA, aae-miR-2940, is selectively downregulated in Aedes albopictus cells. This miRNA is known to upregulate the metalloprotease m41 FtsH gene, which we have also shown to be required for efficient WNV replication. Correspondingly, downregulation of aae-miR-2940 reduced the metalloprotease level and restricted WNV replication. Thus, we have identified a novel miRNA-dependent mechanism of antiviral response to WNV in mosquitoes. IMPORTANCE A detailed understanding of vector-pathogen interactions is essential to address the problems posed by vector-borne diseases.Host and viral miRNAs play an important role in regulating expression of viral and host genes involved in endogenous processes, including antiviral response. There has been no evidence to date for the role of mosquito miRNAs in response to flaviviruses. In this study, we show that downregulation of aae-miR-2940 in mosquito cells acts as a potential antiviral mechanism in the mosquito host to inhibit WNV replication by repressing the expression of the metalloprotease m41 FtsH gene, which is required for efficient WNV replication. This is the first identification of an miRNA-dependent antiviral mechanism in mosquitoes, which inhibits replication of WNV. Our findings should facilitate identification of targets in the mosquito genome that can be utilized to suppress vector population and/or limit WNV replication.

show abstract

Comprehensive profiling of Epstein-Barr virus-encoded miRNA species associated with specific latency types in tumor cells

Cited by 46 publications

References 60 publications

RETRACTED: Pan-viral-microRNA screening identifies interferon inhibition as a common function of diverse viruses

RETRACTED: Pan-viral-microRNA screening identifies interferon inhibition as a common function of diverse viruses

EBV-miR-BART7-3p promotes the EMT and metastasis of nasopharyngeal carcinoma cells by suppressing the tumor suppressor PTEN

Expression of Mosquito MicroRNA Aae-miR-2940-5p Is Downregulated in Response to West Nile Virus Infection To Restrict Viral Replication

Contact Info

Product

Resources

About