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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林中梧(Chung-Wu Lin) | |
| dc.contributor.author | Chien-Yu chen | en |
| dc.contributor.author | 陳建宇 | zh_TW |
| dc.date.accessioned | 2021-06-17T01:21:42Z | - |
| dc.date.available | 2022-08-28 | |
| dc.date.copyright | 2017-08-28 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-08-10 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67156 | - |
| dc.description.abstract | 鼻NK細胞淋巴癌(NNL) 是與EB病毒（EBV）有相關的NK细胞淋巴癌，而T-bet是個重要的轉錄因子，會影響毒殺T細胞或NK細胞interferon-gamma (IFN-γ) 的產生，EB 病毒編碼的miR-BART20-5P 抑制T-bet 而誘導鼻NK 細胞淋巴癌對組織的侵入性。YT cells 是人類EBV+ NK-like淋巴癌的細胞株，為了研究miRNA抑制T-bet轉譯的機制，我們用genome-wide shRNA library來篩選YT cells的方式找到BCL11B shRNA會誘導T-bet表現，之後將Flag-BCL11B-EGFP的表現質體用轉染的方式讓YT cells大量表現BCL11B，透過流式細胞分選儀分選出有EGFP的YT cells進行Western blotting分析，發現其T-bet蛋白表現量比EGFP negative的YT cells低，然而T-bet mRNAs並無顯著差異，接著在luciferase assays中我們發現BCL11B會對T-bet抑制是透過結合在T-bet 3’-UTR，而藉由序列比對分析更進一步發現抑制的結合區可能是位在T-bet 3’-UTR 的GAIT-like domains，之後經由RT-PCR分析來證實GAIT-like element-G4會與BCL11B的zinc finger domains作用。除此之外，我們透過YT cells 來表現His-EGFP-BCL11B、 RRE-T-bet-mRNA, 以及Flag-Rev-EGFP，利用Rev-RRE的作用再次證實BCL11B確實與T-bet mRNA的作用，最後我們合成GAIT-like elements 以及Zinc finger peptides透過pull down assay來計算出dissociation constant (Kd)，這些結果將來會用在設計miRNA 或 peptide類似物或者是zinc finger抑制劑透過干擾BCL11B來減緩NNL的侵入性。 | zh_TW |
| dc.description.abstract | Nasal NK-cell lymphoma (NNL) is an Epstein-Barr virus (EBV)-associated aggressive lymphoma of NK cell origin, endemic in Taiwan. T-bet is the key transcription factor involved in interferon-gamma (IFN-γ) production by cytotoxic T or NK cells. EBV-encoded miR-BART20-5p inhibits T-bet translation and induces an aggressive and invasive behavior of NNL. The YT cell line is a human EBV+ NK-like lymphoma cell line. To investigate the mechanisms of miRNA-mediated T-bet translation inhibition, we transduced a genome-wide shRNA library into YT cells and found that the BCL11B shRNA could up-regulate T-bet expression. An expression vector for Flag-BCL11B-EGFP was transfected into YT cells. After sorting, EGFP positive YT cells had lower expression of T-bet than EGFP negative YT cells by Western blotting, in spite of similar levels of T-bet mRNAs by real-time RT-PCR. Using luciferase assays, we confirmed BCL11B interacts with 3’-untranslated region (UTR) of T-bet. Further analysis showed the presence of GAIT-like domains in the T-bet 3’-UTR. Real-time RT-PCR of precipitated lysate from YT cells overexpressing the zinc fingers of BCL11B confirmed interactions between interferon-gamma-activated inhibitor of translation (GAIT) -like elements and zinc finger domains of BCL11B. Finally, we used synthetic GAIT-like elements and zinc finger peptides in a pull-down assay to obtain a dissociation constant. The data will be used to design miRNA or peptide mimics and zinc finger inhibitor that may ameliorate the invasive behavior of NNL through interfering with BCL11B. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T01:21:42Z (GMT). No. of bitstreams: 1 ntu-106-R04444002-1.pdf: 1903564 bytes, checksum: 8e72b8ba6224e893c6720fa3a34518b3 (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | Contents I
致謝 III 摘要 IV Abstract V Chapter 1: Introduction 1 Chapter 2: Materials and Methods 5 2.1 Plasmid constructs and synthesis of RNA and peptides 5 2.2 Synthesis of G4 and peptide 5 2.3 Cell lines and stable cell lines 5 2.4 Cell sorting and flow cytometry 7 2.5 Western Blotting 7 2.6 Luciferase assay 9 2.7 Real-time RT-PCR 9 2.8 Ni-NTA magnetic beads 10 2.9 G4 RNA pull-down assay by BCL11B or zinc fingers after crosslink (Fig 4C) 11 2.10 G4 RNA pull-down assay by synthetic peptide without crosslink (Fig 5) 12 Chapter 3: Results 14 3.1 Five siRNAs from the genome-wide shRNA Library induce T-bet expression. 14 3.2 BCL11B and TRIM71 inhibit T-bet expression. 14 3.3 Localization of BCL11B and TRIM71 in YT cells. 15 3.4 BCL11B inhibit the luciferase via T-bet 3’-UTR. 15 3.5 GAIT-like elements and BCL11B zinc fingers inhibit T-bet translation. 16 3.6 G4 RNA interacts with the sixth zinc finger of BCL11B 16 3.7 His-EGFP-BCL11B co-precipitates Flag-Rev-EGFP via RRE-T-bet mRNA. 17 Chapter 4: Discussion 19 Chapter 5: Conclusion 24 Figures 25 Reference 39 Appendix 48 | |
| dc.language.iso | en | |
| dc.subject | 鼻自然殺手細胞淋巴癌 | zh_TW |
| dc.subject | EBV病毒 | zh_TW |
| dc.subject | T-bet 轉錄因子 | zh_TW |
| dc.subject | B細胞淋巴癌11B | zh_TW |
| dc.subject | GAIT-like結構 | zh_TW |
| dc.subject | Epstein-Barr virus | en |
| dc.subject | Nasal NK-cell lymphoma | en |
| dc.subject | T-bet | en |
| dc.subject | BCL11B | en |
| dc.subject | GAIT-like domain | en |
| dc.title | 以YT cells作為鼻NK細胞淋巴癌模型探討BCL11B 抑制T-bet mRNA 轉譯 | zh_TW |
| dc.title | BCL11B inhibits translation of T-bet mRNA in YT cells: a model for nasal NK-cell lymphoma | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蕭超隆,蔡錦華,葉德輝 | |
| dc.subject.keyword | 鼻自然殺手細胞淋巴癌,EBV病毒,T-bet 轉錄因子,B細胞淋巴癌11B,GAIT-like結構, | zh_TW |
| dc.subject.keyword | Nasal NK-cell lymphoma,Epstein-Barr virus,T-bet,BCL11B,GAIT-like domain, | en |
| dc.relation.page | 59 | |
| dc.identifier.doi | 10.6342/NTU201702705 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-08-10 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 病理學研究所 | zh_TW |
| 顯示於系所單位： | 病理學科所 | |
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