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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 鄭永銘(Yung -MIng Jeng) | |
| dc.contributor.author | Mo-Fan Chang | en |
| dc.contributor.author | 張莫凡 | zh_TW |
| dc.date.accessioned | 2022-11-25T08:01:37Z | - |
| dc.date.copyright | 2022-01-25 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-01-19 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82879 | - |
| dc.description.abstract | "口腔癌位居於臺灣男性十大癌症中死亡率第四位,每年將近七百人被診斷出口腔癌。口腔癌的五年存活率僅有百分之四十五。ELF-3 (E74 Like ETS Transcription Factor 3)轉錄因子是屬於上皮特異性 ETS 家族。根據之前研究， ELF-3在膀胱癌和膽管癌是抑癌基因，但在結直腸癌中是促癌基因。在這項研究中，我們發現百分之八十三的口腔鱗狀細胞癌中喪失ELF-3表達。我們發現剔除ELF-3 會增進細胞遷移。經由RNA-Seq，我們發現ELF- 3與角質分化和角質化有關。在過量表達ELF-3的SCC-25細胞中發現keratin 1和involucrin被ELF-3上調。為了解 ELF3轉錄調控機制，我們構建了 ELF-3、keratin1和involucrin螢光素酶報導基因之重組載體，並用它們在 SCC-25細胞中進行螢光素酶的活性實驗，我們證實了 ELF-3 上調會促進keratin 1上升。而經TPA (12-O-tetradecanoylphorbol-13-acetate) 和鈣處理過的 SCC-25 會使得ELF-3上升。此外我們使用PathDetct 系統發現 ELF-3誘導了 NF-κB 報導基因的活性，西方墨點法證實NF-κB 的p65次單位的磷酸化也為之增強，證實ELF-3 可活化 NF-κB途徑。總之，我們的結論指出ELF-3 是口腔鱗狀細胞癌的抑癌基因，可抑制腫瘤遷移和促進分化。活化NF-κB的路徑可能是ELF-3增加角質分化的機制。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T08:01:37Z (GMT). No. of bitstreams: 1 U0001-1601202222292000.pdf: 1912353 bytes, checksum: 8a9d630d3f42a4d46d68567a27ede65b (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 口試委員會審定書 I 謝辭 II 中文摘要 III Abstract IV Contents V 1. Introduction 1 1.1 Oral squamous cell carcinoma (OSCC) 1 1.2 ETS family transcription factor 3 1.3 ELF-3 in epithelium 3 1.4 ELF-3 in EMT 4 1.5 ELF-3 in keratinocytes 4 1.6 ELF-3 in carcinoma 5 1.7 Mechanisms of regulating epithelial stratification. 6 1.8 Kallikrein (KLK) in keratinocyte 7 1.9 Protein kinase C 7 1.10 The effects of TPA (12-O-tetra-decanoylphorbol-13-acetate) on keratinocyte. 8 1.11 The aim of this study. 9 2. Martial and Methods 10 2.1 Cell culture 10 2.2 RNA interference for knockdown experiments 10 2.3 Construction of ELF-3 vector 10 2.4 RNA isolation 11 2.5 Reverse Transcription 11 2.6 Real-time PCR 11 2.7 Construction of promoter reporter vectors 11 2.8 Transient luciferase reporter assay 12 2.9 ELF-3 stain in the Oral squamous cell carcinoma. 12 2.10 RNA sequencing 13 2.11 GSEA-based KEGG pathway analysis 13 2.12 Western blot 13 3. Result 15 3.1 Loss of ELF-3 expression in oral squamous cell carcinoma. 15 3.2 Knockdown of ELF-3 promotes invasion in SCC-25 cell line. 15 3.3 Knockdown of ELF3 repressed keratinocyte differentiation. 15 3.4 ELF-3 regulated keratinocyte differentiation genes. 16 3.5 TPA and Calcium treatment of SCC-25 cells induced ELF-3 expression. 16 3.6 ELF-3 promotes promoter was not activity of KRT1 and INV 16 3.7 Identification of upstream regulatory region in ELF-3 promoter 17 3.8 ELF-3 upregulated NF-kB pathway 17 4. Discussion 19 4.1 Loss of ELF-3 promotes OSCC invasion. 19 4.2 ELF-3 regulates keratinocyte differentiation. 19 4.3 ELF-3 upregulated NF-κB in SCC-25 cell line 22 5. Figures and Tables 24 Figure 1. Loss of ELF-3 expression in OSCC. 24 Figure 2. Knockdown ELF-3 promotes invasion in SCC-25 cell lines. (courtesy of Yu-Hsuan Wang) 25 Figure 3. Knockdown of ELF3 repressed keratinocyte differentiation. 27 Figure 4. ELF-3 upregulates keratinocyte differentiation genes. 28 Figure 5. TPA and calcium treatment of SCC-25 cells induces ELF-3 expression……………………………………………………………………….30 Figure 6. ELF-3 promotes promoter not activity of KRT1 and INV. 31 Figure 7. An upstream regulatory region elevates ELF-3 promoter activity. 33 Figure 8. Identification of NF-kB pathway as a downstream pathway. 35 Table.1 The primer for RT-PCR reaction 36 Table 2. Knockdown of ELF-3 regulated gene by RNA sequencing. 37 Table 3. The Gene set enrichment analysis (GESA) pathway of keratinocyte differentiation. 38 Table 4. The transcription factor binding sites (TFBSs) of ELF-3 promoter. 41 6. Reference 42 | |
| dc.language.iso | en | |
| dc.subject | keratin 1 | zh_TW |
| dc.subject | NF-κB | zh_TW |
| dc.subject | 角質分化 | zh_TW |
| dc.subject | ELF-3 | zh_TW |
| dc.subject | 口腔鱗狀細胞癌 | zh_TW |
| dc.subject | NF-κB | en |
| dc.subject | oral squamous cell carcinoma | en |
| dc.subject | ELF-3 | en |
| dc.subject | keratinocyte differentiation | en |
| dc.subject | keratin 1 | en |
| dc.title | ELF-3 調控角質分化及侵襲在於口腔鱗狀細胞癌 | zh_TW |
| dc.title | ELF-3 regulates keratinocyte differentiation and invasion in oral squamous cell carcinoma | en |
| dc.date.schoolyear | 110-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 連晃駿(Kuo-Sheng Cheng),謝明書(Yu-Chieh Kao),(Chih-Ping Chen),(Yi-Li Tseng) | |
| dc.subject.keyword | 口腔鱗狀細胞癌,ELF-3,角質分化,keratin 1,NF-κB, | zh_TW |
| dc.subject.keyword | oral squamous cell carcinoma,ELF-3,keratinocyte differentiation,keratin 1,NF-κB, | en |
| dc.relation.page | 49 | |
| dc.identifier.doi | 10.6342/NTU202200077 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2022-01-19 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 病理學研究所 | zh_TW |
| dc.date.embargo-lift | 2025-01-13 | - |
| 顯示於系所單位： | 病理學科所 | |
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