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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊泮池(Pan-Chyr Yang) | |
| dc.contributor.author | Ya-Ling Chang | en |
| dc.contributor.author | 張雅玲 | zh_TW |
| dc.date.accessioned | 2021-06-16T03:48:53Z | - |
| dc.date.available | 2015-03-12 | |
| dc.date.copyright | 2015-03-12 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-01-26 | |
| dc.identifier.citation | Aubert, M. and Jerome, K.R. (2003). Apoptosis prevention as a mechanism of immune evasion. International reviews of immunology 22, 361-371.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55145 | - |
| dc.description.abstract | 腸病毒71型為一好發於亞洲地區的新興且致命之病原體。細胞凋亡為腸病毒71型感染後最主要的病理特徵．然而，對於腸病毒造成宿主細胞凋亡的分子機制仍未有透澈之研究報導．微核糖核酸(miRNAs)是一個近來發現的新分子，此分子可以透過後轉錄調控方式廣泛地影響生物機能，並且有報導指出微核糖核酸參與病毒致病機轉．本論文欲探討微核糖核酸與信息RNA(mRNA)是否協同調控腸病毒71型感染後所引發之宿主細胞凋亡．利用微核糖核酸與信息RNA表現圖譜加以生物資訊分析等策略，研究腸病毒71型感染後造成細胞凋亡之可能途徑．根據上述策略，可篩選出兩條與細胞凋亡相關之訊息傳遞路線，分別為BAD磷酸化(BAD phosphorylation)與p53所屬(p53-dependent)訊息傳遞．SOS1與GADD45β分別屬於BAD磷酸化與p53所屬訊息傳遞路線，且被預測為微核糖核酸-146a與微核糖核酸-370的標的．利用冷光報導基因試驗與西方墨點法證實微核糖核酸-146a與SOS1以及微核糖核酸-370與GADD45β之間存在負向調控關係．抑制微核糖核酸-146a可恢復SOS1表現量，並輕微減少腸病毒71型感染造成的細胞凋亡．相反地，異位表現微核糖核酸-370會降低因腸病毒71型感染上升的GADD45β的表現量，並減少細胞凋亡．最後，利用微核糖核酸-146a拮抗物與異位表現微核糖核酸-370可顯著減少腸病毒71型引起之細胞凋亡．在此，本研究證明腸病毒71型可藉由調控微核糖核酸表現造成宿主細胞凋亡的分子機制 | zh_TW |
| dc.description.abstract | Enterovirus 71 (EV71) is an emerging life-threatening pathogen particularly in the Asia-Pacific region. The major pathogenic feature in EV71-infected cells is apoptosis. However, which molecular mechanism mainly contributes to EV71-induced apoptosis is not investigated thoroughly. MiRNAs, the newly discovered molecules, govern a wide range of biological functions through post-transcriptional regulation and play roles in viral pathogenesis. Whether miRNAs and mRNAs coordinate to trigger host cell apoptosis in EV71 infection was investigated in this study. We conducted an apoptosis-oriented approach by using both mRNA and miRNA profiling and bioinformatic analysis. We identified two major apoptosis-associated signaling pathways, Bcl2 antagonist of cell death (BAD) phosphorylation and p53-dependent apoptosis pathways, in which Son of sevenless homolog 1 (SOS1) and Growth arrest and DNA damage-inducible protein 45β (GADD45β) were predicted as targets of miR-146a and miR-370, respectively. Luciferase reporter assays and Western blots demonstrated the negative regulation between miR-146a and SOS1 and between miR-370 and GADD45β. Silencing of miR-146a restored SOS1 expression and partially attenuated EV71 infection-induced apoptosis. Conversely, ectopic expression of miR-370 decreased virus infection-induced GADD45β expression and also diminished apoptosis. Finally, the co-expression of antagomiR-146a and miR-370 contributed to attenuating EV71 infection-induced apoptosis. Herein we clearly demonstrate a new mechanism that EV71-induced cell apoptosis is partly governed by altered miRNAs.
| en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T03:48:53Z (GMT). No. of bitstreams: 1 ntu-104-D95448002-1.pdf: 6105869 bytes, checksum: ec83398e0990a8386119e697e7405472 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 口試委員會審定書 4
中文摘要 5 Abstract 6 Introduction 8 Results 13 EV71 infection induces cell apoptosis 13 Reciprocal Interaction of miRNAs and mRNAs contributes to EV71 infection-induced apoptosis 14 SOS1 expression is suppressed by EV71 infection-induced miR-146a 17 GADD45β expression is induced by EV71 infection-suppressed miR-370 18 miR-146a and miR-370 signaling cascades are ubiquitous in EV71-infected tissues 19 Neutralization of virus infection-induced miR-146a suppresses apoptotic mediators and restores the anti-apoptotic indicator 20 Ectopic expression of miR-370 inhibits apoptotic mediators and rescues the anti-apoptotic indicator 21 AntagomiR-146a and miR-370 both exhibit inhibitory effects on EV71-induced apoptosis 22 Discussion 26 Experimental procedures 34 Cell Cultures and Virus Infection 34 RNA Extraction and miRNA Profiling 34 Oligonucleotide Microarray Analysis 35 Functional Ontology Enrichment and Signaling Pathways Analysis 36 Individual Real-Time RT PCR 37 Western Blot 38 Luciferase Assay 38 Plasmid Constructions 39 AntagomiR Transfection 40 Cytopathic Effect Quantification 40 Flow Cytometric Analysis 41 TUNEL Assay 41 Statistical Analysis 42 References 43 | |
| dc.language.iso | en | |
| dc.subject | 微核糖核酸-370 | zh_TW |
| dc.subject | 微核糖核酸-146a | zh_TW |
| dc.subject | miR-146a | en |
| dc.subject | miR-370 | en |
| dc.title | 微核糖核酸-146a和微核糖核酸-370以SOS1和GADD45b當作標的共同調控被腸病毒71型感染後的細胞凋亡 | zh_TW |
| dc.title | miR-146a and miR-370 coordinate Enterovirus 71-induced cell apoptosis through targeting SOS1 and GADD45β | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 呂勝春,李芳仁,俞松良,吳君泰 | |
| dc.subject.keyword | 微核糖核酸-146a,微核糖核酸-370, | zh_TW |
| dc.subject.keyword | miR-146a,miR-370, | en |
| dc.relation.page | 86 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-01-26 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
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