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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 林中梧 | zh_TW |
| dc.contributor.author | 王明彥 | zh_TW |
| dc.contributor.author | Ming-Yen Wang | en |
| dc.date.accessioned | 2021-07-11T15:39:19Z | - |
| dc.date.available | 2024-02-28 | - |
| dc.date.copyright | 2018-10-11 | - |
| dc.date.issued | 2018 | - |
| dc.date.submitted | 2002-01-01 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79045 | - |
| dc.description.abstract | 鼻 NK 細胞淋巴癌 (NNL) 是感染 Epstein-Barr 病毒 （EBV） 的侵襲性淋巴癌。 T-bet 是 NK 細胞產生 γ 型干擾素的關鍵轉錄因子。 EBV 編碼的 miR-BART20-5p 抑制了 T-bet 轉譯，同時抑制 p53 並造成 NNL 的侵襲行為。透過全基因 shRNA 文庫篩選，我們篩選出五個 shRNAs可以誘導 T-bet 表現。因此，受 shRNAs 標的的基因可能參與 miR-BART20-5p 抑制 T-bet 的路徑。其中，BCL11B 是一個可能的標的基因並且扮演抑制 T-bet的調節因子，透過與 T-bet 3'-UTR 的交互作用進而抑制 T-bet。我們預估BCL11B 的模擬蛋白可以阻斷 BCL11B 的調節功能並誘導 NNL 的 T-bet 作為治療。
以 BCL11B 鋅指結構域（ZFD）-EGFP 轉染的 YT 細胞可誘導 T-bet 和 p53 的表現。在我們的初步數據中，我們提出 ZFD 做為 NNL 的治療藥物的可能性。在相關文獻中，KIR2DL4 （CD158d） 在 NNL 中具有較高的表現量，而且人類白血球抗原 –G （HLA-G） 為 CD158d 的配體。結合 HLA-G 的 ZFD 可以更有效地誘導 YT 細胞凋亡。除此之外，透過細菌純化的 HLA-G-EGFP-ZFD 蛋白可在較高濃度下誘導 YT 細胞凋亡或壞死。 在進一步的實驗當中，我們將 HLA-G-EGFP-ZFD 的純化蛋白靜脈注射到動物模型中，發現此蛋白具有抑制腫瘤生長的效果。因此，我們預期這些結果的運用將可能開發作為 NNL 的替代治療。 | zh_TW |
| dc.description.abstract | Nasal NK-cell lymphoma (NNL) is an aggressive lymphoma infected with Epstein-Barr virus (EBV). T-bet is a key transcription factor for production of interferon-gamma on NK cells. EBV-encoded miR-BART20-5p inhibits T-bet translation with secondary suppression of p53 and causes an invasive behavior of NNL. By genome-wide shRNA library screening, we identified five shRNAs which could induce T-bet. ShRNAs-targeted genes may engage in the T-bet inhibition pathway triggered by miR-BART20-5p. BCL11B was a potential target gene and it was identified as a regulator to inhibit T-bet via interaction with 3’-UTR. We estimated that a mimic protein of BCL11B could block the regulator function of BCL11B and induce T-bet on NNL as a treatment.
T-bet and p53 were induced on BCL11B zinc finger domains (ZFD)-EGFP transfected YT cells. In the preliminary data, we propose that ZFD might be a therapeutic for NNL. In the relevant literature, KIR2DL4 (CD158d) has higher expression on NNL and human leukocyte antigen -G (HLA-G) was known as CD158d ligand. HLA-G conjugated ZFD can induce YT cells apoptosis more effectively. In addition, HLA-G-EGFP-ZFD protein purified from bacteria can induce apoptosis or necrosis on YT cells under higher concentration. In the further experiments, we intravenously injected HLA-G-EGFP-ZFD into animal model and the tumor growth was inhibited. It is expected that we could use these results to develop an alternative therapeutic trial for NNL. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:39:19Z (GMT). No. of bitstreams: 1 ntu-107-R05444006-1.pdf: 4686105 bytes, checksum: f902cbac6e0028c1dd81d91f87acbeff (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | Contents....... I
誌謝... III 中文摘要 ...IV Abstract....... V Chapter 1: Introduction. 1 Chapter 2: Materials and Methods....... 9 2.1 Cell culture....... 9 2.2 Preparation of competent cells E. coli JM109 strain (ARROWTEC, Cat. No. A5828100) or E. coli Rosetta (DE3) strain (Novagen, Cat. No. 70954)....... 10 2.3 Transformation..... 10 2.4 Miniprep... 11 2.5 Silica based maxiprep plasmid extraction[57]....... 11 2.6 Plasmid constructs (Fig 1A)........ 14 2.7 Transfection of YT cells (Fig 1B).. 14 2.8 Sorting (Fig 1C)... 15 2.9 Western blotting (Fig 1D).. 15 2.10 Eukaryotic protein expression in 293T cells (Fig 2A, 2B).... 17 2.11 Flow cytometry for Annexin-V & PI (Fig 2C & 3D)... 19 2.12 Plasmid constructs (Fig 3A)....... 20 2.13 Bacterial system for protein expression (Fig 3A).. 20 2.14 Large Scale purification (Fig 3B). 21 2.15 Fine needle aspiration for smears and cell blocks (Fig 4C & D)........ 23 2.16 Autopsy (Fig 4 C & D)..... 24 2.17 Immunohistochemistry (Fig 4 E & F)........ 24 Chapter 3: Results..... 27 3.1 Overexpression of Zinc Finger Domain (ZFD) induces T-bet and p53 in YT cells.... 27 3.2 EGFP-ZFD-HLA-G in culture medium induces death of YT cells.. 28 3.3 HLA-G-EGFP-ZFD may induce concentration-dependent apoptosis /or death of YT cells........ 29 3.4 Systemic HLA-G-EGFP-ZFD injection inhibits invasion and growth of YT cells implanted subcutaneously in SCID mice ...........30 Chapter 4: Discussion.. 32 Chapter 5: Conclusion.. 37 Figures ................38 Reference.............. 63 Appendix............... 72 | - |
| dc.language.iso | en | - |
| dc.title | BCL11B 模擬蛋白於鼻 NK 細胞淋巴癌誘導 T-bet | zh_TW |
| dc.title | BCL11B mimic protein induces T-bet in nasal NK-cell lymphoma | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 106-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 黃聖懿;謝明書 | zh_TW |
| dc.contributor.oralexamcommittee | ;; | en |
| dc.subject.keyword | 鼻NK 細胞淋巴癌,T-bet,BCL11B 鋅指結構域,HLA-G,細胞凋亡, | zh_TW |
| dc.subject.keyword | Nasal NK-cell lymphoma,T-bet,BCL11B zinc finger domains (ZFD),HLA-G,apoptosis., | en |
| dc.relation.page | 103 | - |
| dc.identifier.doi | 10.6342/NTU201803241 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2018-08-14 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 病理學研究所 | - |
| dc.date.embargo-lift | 2023-10-11 | - |
| Appears in Collections: | 病理學科所 | |
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