Epstein-Barr Virus-Encoded MicroRNA BART15-3p Promotes Cell Apoptosis Partially by Targeting BRUCE

Choi, Hoyun; Lee, Hanna; Kim, Sae Rom; Gho, Yong Song; Lee, Suk Kyeong

doi:10.1128/jvi.03159-12

Cited by 98 publications

(85 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Antisense knockdown of TOMM22 has been shown to inhibit the association of the pro-apoptotic protein Bcl-2-associated X (BAX) with mitochondria and thus prevent BAX-induced apoptosis (Bellot et al, 2007;Dolken et al, 2010). MiR-BART15-3p can induce apoptosis partially by inhibiting an apoptosis inhibitor, BIR repeatcontaining ubiquitin-conjugating enzyme (BRUCE) (Choi et al, 2013). These reports show that EBV miRNAs help to maintain the viral latent status in the infected cells by preventing the host immune response.…”

Section: Ebv Mirnas Suppress Apoptosis Of Infected Cells To Maintain mentioning

confidence: 83%

“…EBV-transformed lymphoblastoid B cells also secrete several viral miRNAs, including miR-BHRF1-1, miR-BHRF1-2, miR-BART1-3p, miR-BART1-5p, and miR-BART2-5p (Meckes et al, 2010). EBV-infected B lymphocytes are able to secrete miR-BART15 (Choi et al, 2013). The exosomal miR-BART15 provides a favorable microenvironment for the growth of EBV-associated tumors.…”

Section: Ebv Regulates the Inflammatory Tumor Microenvironment Via MImentioning

confidence: 99%

See 1 more Smart Citation

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

Zuo

Yue

et al. 2017

Virol. Sin.

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

Section: Ebv Mirnas Suppress Apoptosis Of Infected Cells To Maintain mentioning

confidence: 83%

Section: Ebv Regulates the Inflammatory Tumor Microenvironment Via MImentioning

confidence: 99%

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

Zuo

Yue

et al. 2017

Virol. Sin.

View full text Add to dashboard Cite

show abstract

“…For example, Marquitz et al demonstrated that the expression of the proapoptotic protein Bim was downregulated by several EBV miRNAs located in ebv-miR-BART cluster 1, to which ebv-miR-BART4-5p belongs (29). Several miRNAs in cluster 1 have been demonstrated to show both antiapoptotic and proapoptotic effects, and it is possible that several EBV miRNAs interact to cooperatively regulate apoptosis via different apoptosis-related proteins (30,36,37). Further work is necessary to clarify the complex mechanism by which EBV miRNAs regulate apoptosis-related proteins and the potential relationship with latent genes and tumor subtypes.…”

Section: Discussionmentioning

confidence: 99%

Profiling of Virus-Encoded MicroRNAs in Epstein-Barr Virus-Associated Gastric Carcinoma and Their Roles in Gastric Carcinogenesis

Shinozaki‐Ushiku

Kunita

Isogai

et al. 2015

J Virol

105

104

View full text Add to dashboard Cite

Epstein-Barr virus (EBV) is one of the major oncogenic viruses and is found in nearly 10% of gastric carcinomas. EBV is known to encode its own microRNAs (miRNAs); however, their roles have not been fully investigated. The present report is the largest series to comprehensively profile the expression of 44 known EBV miRNAs in tissue samples from patients with EBV-associated gastric carcinoma. Several miRNAs were highly expressed in EBV-associated gastric carcinoma, and in silico analysis revealed that the target genes of these EBV miRNAs had functions associated with cancer-related pathways, especially the regulation of apoptosis. Apoptosis was reduced in EBV-associated gastric carcinoma tissue samples, and gastric carcinoma cell lines infected with EBV exhibited downregulation of the proapoptotic protein Bid (the BH3-interacting domain death agonist), a member of the Bcl-2 family. The luciferase activity of the reporter vector containing the 3= untranslated region of BID was inhibited by an ebv-miR-BART4-5p mimic in gastric cancer cell lines. Transfection of an ebvmiR-BART4-5p mimic reduced Bid expression in EBV-negative cell lines, leading to reduced apoptosis under serum deprivation. The inhibition of ebv-miR-BART4-5p expression was associated with partial recovery of Bid levels in EBV-positive cell lines. The results demonstrated the antiapoptotic role of EBV miRNA via regulation of Bid expression in EBV-associated gastric carcinoma. These findings provide novel insights in the roles of EBV miRNAs in gastric carcinogenesis, which would be a potential therapeutic target. IMPORTANCEThis report is the largest series to comprehensively profile the expression of 44 known EBV miRNAs in clinical samples from EBV-associated gastric carcinoma patients. Of the EBV miRNAs, ebv-miR-BART4-5p plays an important role in gastric carcinogenesis via regulation of apoptosis. E pstein-Barr virus (EBV) is one of the major oncogenic viruses inducing various kinds of malignancies in humans. The virus originally was isolated from Burkitt's lymphoma and is associated with other hematopoietic tumors, including Hodgkin's lymphoma, extranodal nasal-type NK/T-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), and lymphoproliferative disorders in immunosuppressed patients, as well as some epithelial malignancies, such as nasopharyngeal carcinoma (NPC) and gastric carcinoma (1-3). Nearly 10% of all gastric carcinomas are associated with EBV infection and form a distinct subtype of disease, exhibiting characteristic clinicopathological features (4).Several studies have investigated the roles played by EBV in carcinogenesis and have sought to show that EBV gene transcripts, including EBV nuclear antigen 2 (EBNA2) or latent membrane protein 1 (LMP1), disturb signal transduction in host cells, causing immortalization or transformation (5). Although these studies have shed light on the oncogenic properties of EBV, many unsolved problems remain.Recently, a novel class of small, noncoding RNA molecules, termed microRNAs (miRNAs), has ...

show abstract

“…Epstein-Barr Virus (EBV) microRNAs (miRNAs) processed from the BHRF1 and BamHI A rightward (BART) transcript, miR-BART15-3p, targets the 3' untranslated region (UTR) of BIRC6. miR-BART15-3p inhibits the translation of BIRC6 protein in EBV-infected gastric carcinoma cells and contributes to host cells apoptosis induction (Choi et al, 2013). In muscle, prostaglandin F2a upregulates BIRC6 which promotes muscle cell survival and growth (Jansen and Pavlath, 2008).…”

Section: Regulation Of Birc6mentioning

confidence: 99%

BIRC6 (Baculoviral IAP repeat-containing 6)

Luk¹,

Wang²

2017

Atlas of Genetics and Cytogenetics in Oncology and Haematology

View full text Add to dashboard Cite

The BIRC6 gene (BRUCE/APOLLON) encodes the cytoplasmic protein BIRC6 in mammals, consisting of a single N-terminal baculoviral IAP repeat (BIR) domain and a C-terminal ubiquitin-conjugating (UBC) domain. Of the huge protein size at 528 kDa, BIRC6 demonstrated pleiotropic functions including inhibition of apoptosis, cytoprotection, regulation of cytokinesis, mitosis, autophagy and neutrophil differentiation. With the BIR domain, BIRC6 is defined as a member of the Inhibitor of Apoptosis (IAP) family. Through its BIR domain, BIRC6 binds to active caspases, including caspases-3, 6, 7 and 9 and accounts for its ability to inhibit the caspase cascade and ultimately apoptosis. The UBC domain has chimeric E2/E3 ubiquitin ligase activity where it facilitates proteosomal degradation of various proteins, including pro-apoptotic proteins p53, caspases, Smac and mitotic regulator cyclin A. More importantly, the UBC domain plays an indispensable role in embryonic development in mammals and spermatogenesis in Drosophila. Increasing evidence supports the cancer promoting role of BIRC6. Elevated BIRC6 expression has been found in a variety of cancers and was shown to contribute to treatment resistance.

show abstract

Epstein-Barr Virus-Encoded MicroRNA BART15-3p Promotes Cell Apoptosis Partially by Targeting BRUCE

Cited by 98 publications

References 41 publications

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

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

Profiling of Virus-Encoded MicroRNAs in Epstein-Barr Virus-Associated Gastric Carcinoma and Their Roles in Gastric Carcinogenesis

BIRC6 (Baculoviral IAP repeat-containing 6)

Contact Info

Product

Resources

About