https://scholars.lib.ntu.edu.tw/handle/123456789/468858
標題: | Epstein-barr virus-encoded miR-BART20-5p inhibits t-bet translation with secondary suppression of p53 in invasive nasal NK/T-cell lymphoma | 作者: | Lin T.-C. Liu T.-Y. Hsu S.-M. CHUNG-WU LIN |
公開日期: | 2013 | 卷: | 182 | 期: | 5 | 起(迄)頁: | 1865-1875 | 來源出版物: | American Journal of Pathology | 摘要: | Nasal NK/T-cell lymphoma (NNL) is an Epstein-Barr virus (EBV)-associated lymphoma derived from cytotoxic NK or T cells of the nasal mucosa. NNLs are noninvasive in the earliest stage, and become invasive with disease progression. The EBV encodes at least 44 miRNAs, whose functions in the pathogenesis of NNL are mostly unknown. We evaluated the levels of 39 EBV-encoded miRNAs with quantitative real-time RT-PCR in a series of 20 noninvasive NNLs and 20 invasive NNLs. miR-BART20-5p was associated most strongly with invasion (P ? 0.001), and lack of T-bet, the master transcription factor for cytotoxic NK cells. However, we identified T-bet (official symbol, TBX21) transcripts in T-bet-negative NNLs, implying a block in the translation of T-bet by miR-BART20-5p. In co-transfection experiments, miR-BART20-5p inhibited T-bet translation in both non-Hodgkin and Hodgkin lymphoma cell lines. Endogenous mir-BART20-5p also inhibited translation of T-bet in EBV-infected YT lymphoma cells of NK-cell origin. Induction of T-bet in YT cells up-regulated p53, leading to increased sensitivity in response to doxorubicin. Finally, YT cells transplanted into severe combined immunodeficiency mice had an invasive behavior. Taken together, we conclude that EBV-encoded miR-BART20-5p inhibits T-bet translation with secondary suppression of p53 in invasive nasal NK/T-cell lymphoma. An antagomir to miR-BART20-5p might be an effective therapeutic agent through induction of T-bet and p53. Copyright ? 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84876565748&doi=10.1016%2fj.ajpath.2013.01.025&partnerID=40&md5=7bf5606a1a7530df95435e2bea243bbc https://scholars.lib.ntu.edu.tw/handle/123456789/468858 |
ISSN: | 0002-9440 | DOI: | 10.1016/j.ajpath.2013.01.025 | SDG/關鍵字: | antagomir; antineoplastic agent; doxorubicin; microRNA; mir bart20 5p; protein p53; transcription factor T bet; unclassified drug; 3' untranslated region; 5' untranslated region; animal behavior; animal cell; animal experiment; animal model; animal tissue; apoptosis; article; cancer cell culture; cancer invasion; competitive inhibition; controlled study; drug efficacy; drug sensitivity; Epstein Barr virus; genetic transfection; Hodgkin disease; immunohistochemistry; microarray analysis; mouse; nasal NK T cell lymphoma; NK T cell lymphoma; nonhodgkin lymphoma; nonhuman; nose cancer; nose mucosa; priority journal; reverse transcription polymerase chain reaction; upregulation; wild type; Animals; Base Sequence; Cell Line, Tumor; Doxorubicin; Gene Expression Regulation, Neoplastic; Herpesvirus 4, Human; Humans; Lymphoma, Extranodal NK-T-Cell; Mice; Mice, SCID; MicroRNAs; Molecular Sequence Data; Neoplasm Invasiveness; Protein Biosynthesis; T-Box Domain Proteins; Transfection; Tumor Suppressor Protein p53; Up-Regulation |
顯示於: | 病理學科所 |
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