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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 俞松良(Sung-Liang Yu) | |
dc.contributor.author | Pin-Yen Hsu | en |
dc.contributor.author | 徐彬嚴 | zh_TW |
dc.date.accessioned | 2021-05-19T17:58:32Z | - |
dc.date.available | 2021-08-26 | |
dc.date.available | 2021-05-19T17:58:32Z | - |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-04 | |
dc.identifier.citation | References
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7916 | - |
dc.description.abstract | 越來越多的證據指出小分子核糖核酸在癌症形成的形成與侵襲過程中扮演重要的角色。經由我們將十六個肺腺癌細胞株各自所有的小分子核糖核酸 (miRNA) 表現以及細胞本身侵襲能力綜合比較之後,發現六個和細胞侵襲能力相關的miRNA,接者,藉由一個包含九十八個肺腺癌病人的臨床試驗我們發現miR-10a*是一個以細胞侵襲能力為依據的預後指標基因。另外,我們是目前第一個驗證組蛋白去乙醯酶5 (HDAC5) 是miR-10a*的直接目標物。HDAC5可能是藉由抑制轉錄因子AP-1的表現來達到負向調控基質金屬蛋白酵素-2和基質金屬蛋白酵素-9的表現。此外,我們讓細胞過度表現miR-10a*之後可以藉由其基因微陣列晶片結果發現排名第四名的訊息路徑是和YAP相關,我們先前研究發現在有高度家族顯性的肺腺癌中YAP1 R331W會是個容易罹患的對偶基因點突變,在此篇研究裡面我們發現YAP1 R331W本身和WT組別比較之後可能是藉由增加YAP1在細胞核內的累積量、降低YAP1 S127磷酸化程度、增強YAP1-TEAD4的相互作用和提高YAP1蛋白的穩定程度等多項因素來達成在動物實驗中觀察到YAP1 R331W具有較強的腫瘤生成能力。我們在此篇研究清楚地驗證出致癌性基因miR-10a*和YAP1在肺腺癌中的致癌機制。 | zh_TW |
dc.description.abstract | The growing evidences implied that miRNAs play important roles in different states of cancers as well as cancer invasion. Comparison between the miRNA expression profiles and the invasiveness of 16 lung adenocarcinoma cells, 6 invasion-related miRNAs were found. Using a cohort of 98-lung adenocarcinoma patients, we identified miR-10a* is an invasion-based prognostic gene in lung adenocarcinoma. Besides, we firstly found that histone deacetylases 5 (HDAC5) is a direct target of miR-10a* and it also is important for miR-10a*-promoted invasiveness. HDAC5 might down-regulate MMP-2 and MMP-9 expression through down-regulation of transcription factor AP-1. Besides, YAP signaling pathway was ranked number 4 of the array result of miR-10a* overexpressing cells. Before, we identified that YAP1 R331W is an allele predisposed for lung adenocarcinoma with high familial penetrance. We found YAP1 R331W might increase tumorigenesis in vitro and in vivo through higher YAP1 nuclear accumulation, lower phosphorylation of YAP1 Ser127, stronger YAP1-TEAD4 interaction and better protein stability than WT group. We clearly demonstrated the mechanism of oncogenic miRNA-10a* and YAP1 in metastasis and tumorigenesis in lung adenocarcinoma. | en |
dc.description.provenance | Made available in DSpace on 2021-05-19T17:58:32Z (GMT). No. of bitstreams: 1 ntu-105-D98424007-1.pdf: 6350198 bytes, checksum: efd136bb67eb6d425dce175f1af29c56 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | Content
口試委員審定書 I 謝誌 I 中文摘要 II Abstract III List of Figures VIII List of Tables XI Introduction 1 Metastasis 1 Lung cancer 1 MiRNAs and tumor metastasis 2 HDACs and cancer 3 Driver mutations in cancer 4 Hippo signaling pathway 5 Motivation and purpose 6 Materials and methods 7 Cell culture 7 Human lung adenocarcinoma patients and tumor specimens 7 Invasion assay 8 Real-time quantitative PCR (qRT-PCR) 8 MicroRNA expression microarray 9 miRNA precursor and siRNA transfection 10 Plasmid Construction 11 mRNA expression microarray 12 Luciferase reporter assay 13 Western blot assays 13 Gelatin zymography 14 Immunohistochemistry Staining 15 shRNA lentivirus infection 15 Colony formation assay 16 Xenograft tumor models 16 Immunoprecipitation 17 Nuclear and cytoplasmic extraction 18 Statistical analysis 18 Results 19 Part-I 19 MiR-10a* expression associates with poor survival in lung adenocarcinoma 19 MiR-10a* promotes cell invasion in vitro 20 HDAC5 is a miR-10a* target 21 HDAC5 attenuates the invasive ability of lung adenocarcinoma cells 23 Mechanism of miR-10a*-induced invasiveness 25 Part-II 27 YAP1 R331W mutation increased colony formation in vitro and in vivo 27 YAP1 R331W mutation promoted invasiveness in vitro 29 The potential YAP1 R331W mediated-mechanisms in lung adenocarcinoma 30 Discussion 31 Part-I 31 Part-II 35 References 75 | |
dc.language.iso | en | |
dc.title | 肺腺癌中致癌基因miRNA-10a*和YAP1在轉移過程
及腫瘤生成過程之機制探討 | zh_TW |
dc.title | The Mechanism of Oncogenic miRNA-10a* and YAP1 in Metastasis and Tumorigenesis in Lung Adenocarcinoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 周玉山(Yuh-Shan Jou),楊慕華(Muh-Hwa Yang),蘇剛毅(Kang-Yi Su),華國泰(Kuo-Tai Hua),潘思樺(Szu-Hua Pan) | |
dc.subject.keyword | 轉移,致癌性小分子核糖核酸,組蛋白去乙醯?5,Hippo訊息傳遞路徑,YAP1 絲胺酸127, | zh_TW |
dc.subject.keyword | Metastasis,oncogenic miRNA,HDAC5,Hippo pathway,YAP1 Ser127, | en |
dc.relation.page | 80 | |
dc.identifier.doi | 10.6342/NTU201601636 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2016-08-04 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
顯示於系所單位: | 醫學檢驗暨生物技術學系 |
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