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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳為堅 | |
| dc.contributor.author | Mu-Jung Shieu | en |
| dc.contributor.author | 薛牧融 | zh_TW |
| dc.date.accessioned | 2021-06-16T02:26:32Z | - |
| dc.date.available | 2020-09-14 | |
| dc.date.copyright | 2015-09-14 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-05 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53623 | - |
| dc.description.abstract | 背景與目的：微小核醣核酸表現異常被認為是有潛力可發展成思覺失調症的臨床生物指標，先前研究利用微陣列技術以及即時聚合酶鏈式反應顯示: hsa-miR-34a為思覺失調症患者周邊血液內找出七個表現異常的微小核醣核酸中最顯著表現量偏高的微小核醣核酸。本篇研究主要目的為1)從生物資訊系統中辨認一個miR-34a管控的基因，此基因亦在中樞神經系統中表現，此外此基因在目前文獻中與思覺失調症相關；2)利用報導基因檢測驗證此基因為miR-34a之標的基因，3)量測思覺失調症病人與健康對照組血液中miR-34a與其標的基因的表現量。 方法：利用資料庫(miRGen)搜尋潛miR-34a之標的基因，之後比對全基因組關聯研究資料庫中(GWAS)與思覺失調症相關之基因。依照是否在生物資訊系統中、基因功能、GWAS研究中使用中國人口、GWAS研究中此基因之顯著性之標準，選定絡絲蛋白(Reelin)為本篇研究選定之標的基因。此外，我們利用西方點墨法量測在神經母細胞瘤細胞株不同轉染組(包括對照組、miR-34a模擬組、miR-34a 抑制組)中絡絲蛋白之表現量。利用絡絲蛋白3'非轉譯區之報導基因檢測轉染miR-34a模擬組以及miR-34a 抑制組。最後我們使用11位思覺失調症患者以及年齡性別配對的健康對照組量測其周邊血液之miR-34a以及絡絲蛋白之表現量。 結果：利用西方墨點法發現在微小核醣核酸miR-34a 模擬組的絡絲蛋白基因表現量有劑量效應般的抑制情形，此外在報導基因檢測實驗當中證實微小核醣核酸miR-34a與絡絲蛋白的3'非轉譯區的互動。在思覺失調症患者當中有較高的miR-34a表現量之趨勢。然而，在思覺失調症患者以及健康對照組的周邊血液中無法測量到絡絲蛋白之表現量。在思覺失調症患者與健康對照組中並沒有觀察到miR-34a和絡絲蛋白表現量之顯著差異，但是在絡絲蛋白330 kDa 思覺失調症患者呈現邊際顯著的較高表現量。此外，本研究觀察到在初始收案時，絡絲蛋白表現量(除了330 kDa)與miR-34a的表現量呈現正相關。 討論：本篇研究證實在細胞株當中，絡絲蛋白被miR-34a所調控，然而，在本篇所使用的人類樣本中的周邊血液中無法測量到絡絲蛋白之表現量。進一步量測絡絲蛋白在腦組織中表現量來評估絡絲蛋白在中樞神經系統中表現量異常是否為miR-34a所調控對於深入了解思覺失調症患者的病理生理學有所助益。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-16T02:26:32Z (GMT). No. of bitstreams: 1 ntu-104-R01849048-1.pdf: 903166 bytes, checksum: 5ff1c6df15d3fe4ffdbed08d2f2af42e (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 論文口試委員審定書 II 誌謝 III 中文摘要 IV ABSTRACT VI CONTENTS VIII LIST OF TABLES AND FIGURES X 1 INTRODUCTION 1 2 METHOD 5 2.1 Participants 5 2.2 miR-34a target prediction 5 2.3 PBMCs isolation 6 2.4 Cell culture 6 2.5 Transfection 7 2.6 Western blotting 7 2.7 microRNA quantification by RT-PCR 8 2.8 Target Gene Reporter Assay 9 2.9 Statistical analysis 9 3 RESULTS 11 3.1 Prediction of miR-34a target genes 11 3.2 Repression of RELN expression in vitro 11 3.3 Biological activity of miR-34a in RELN 3’UTR 12 3.4 miRNA and RELN expression in schizophrenia patients and healthy controls 13 4 DISCUSSION 15 REFERENCES 20 APPENDICES Table A1. Oligonucleotide sequences of experiment materials 39 Table A2. miR-34a target genes consistent in “miRGen” that have been reported in schizophrenia GWAS studies from November, 2008 to April, 2014.. 40 Figure A1. Undetectable expression level of RELN in SH-SY5Y and SK-N-DZ cell lines by western blot. 42 Figure A2. Troubleshooting of Western blotting to detect RELN. 43 | |
| dc.language.iso | en | |
| dc.subject | 微小核醣核酸34a | zh_TW |
| dc.subject | 絡絲蛋白 | zh_TW |
| dc.subject | 報導基因檢測 | zh_TW |
| dc.subject | 思覺失調症 | zh_TW |
| dc.subject | reporter gene assay | en |
| dc.subject | schizophrenia | en |
| dc.subject | hsa-miR-34a | en |
| dc.title | 思覺失調症患者周邊血液中表現偏高的微小核醣核酸miR-34a與其標的基因絡絲蛋白:生物資訊系統辨認與報導基因檢測驗證 | zh_TW |
| dc.title | Up-regulated microRNA miR-34a in Peripheral Blood of Patients with Schizophrenia and Reelin as Its Target Gene: Identification from Algorithms and Validation in Reporter Gene Assays | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 俞松良,郭柏秀,劉智民 | |
| dc.subject.keyword | 思覺失調症,報導基因檢測,微小核醣核酸34a,絡絲蛋白, | zh_TW |
| dc.subject.keyword | schizophrenia,reporter gene assay,hsa-miR-34a, | en |
| dc.relation.page | 43 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-05 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
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