| Title | EBV-miR-BHRF1-2 targets PRDM1/Blimp1: potential role in EBV lymphomagenesis. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Ma J, Nie K, Redmond D, Liu Y, Elemento O, Knowles DM, Tam W |
| Journal | Leukemia |
| Volume | 30 |
| Issue | 3 |
| Pagination | 594-604 |
| Date Published | 2016 Mar |
| ISSN | 1476-5551 |
| Keywords | 3' Untranslated Regions, Base Sequence, Binding Sites, Carcinogenesis, Cell Cycle Checkpoints, Cell Line, Tumor, Epstein-Barr Virus Infections, Gene Expression Regulation, Neoplastic, Herpesvirus 4, Human, Host-Pathogen Interactions, Humans, Lymphoma, Large B-Cell, Diffuse, MicroRNAs, Molecular Sequence Data, Paraffin Embedding, Positive Regulatory Domain I-Binding Factor 1, Protein Isoforms, Repressor Proteins, RNA, Small Interfering, RNA, Small Nucleolar, Signal Transduction, Tissue Fixation, Viral Proteins |
| Abstract | <p>PRDM1/Blimp1, a master regulator of B-cell terminal differentiation, has been identified as a tumor suppressor gene in aggressive lymphomas, including diffuse large B-cell lymphoma (DLBCL). It has been shown in DLBCL and Hodgkin lymphoma that PRDM1 is downregulated by cellular microRNAs. In this study, we identify the Epstein-Barr virus (EBV) microRNA (miRNA), EBV-miR-BHRF1-2, as a viral miRNA regulator of PRDM1. EBV-miR-BHRF1-2 repressed luciferase reporter activity by specific interaction with the seed region within the PRDM1 3' untranslated region. EBV-miR-BHRF1-2 inhibition upregulated PRDM1 protein expression in lymphoblastoid cell lines (LCL), supporting a role of miR-BHRF1-2 in PRDM1 downregulation in vivo. Discordance of PRDM1 messenger RNA and protein expressions is associated with high EBV-miR-BHRF1-2 levels in LCLs and primary post-transplant EBV-positive DLBCL. Enforced expression of PRDM1-induced apoptosis and cell cycle arrest in LCL cells. Inhibition of EBV-miR-BHRF1-2 negatively regulates cell cycle and decreases expression of SCARNA20, a small nucleolar RNA that is also downregulated by PRDM1 overexpression. The interaction between EBV-miR-BHRF1-2 and PRDM1 may be one of the mechanisms by which EBV-miR-BHRF1-2 promotes EBV lymphomagenesis. Our results support the potential of EBV-miR-BHRF1-2 as a therapeutic target in EBV-associated lymphoma.</p> |
| DOI | 10.1038/leu.2015.285 |
| Alternate Journal | Leukemia |
| PubMed ID | 26530011 |
| PubMed Central ID | PMC4777778 |