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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賴亮全(Liang-Chuan Lai) | |
| dc.contributor.author | En-Ching Luo | en |
| dc.contributor.author | 羅恩晴 | zh_TW |
| dc.date.accessioned | 2021-06-16T08:28:34Z | - |
| dc.date.available | 2016-02-25 | |
| dc.date.copyright | 2014-02-25 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2014-01-14 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58742 | - |
| dc.description.abstract | Hypoxia and reoxygenation were characteristic features of solid tumors, which resulted in the complex changes in cellular energy charge, oxidant generating systems, and antioxidant defenses. These changes led to an oxidative stress, tissue damage, and activation of stress-response genes. Although, a protective state would be induced to against reactive oxygen species, little was known about the mechanism of protection. Previously, our lab identified that N-myc downstream-regulated gene 1 (NDRG1) was strongly up-regulated under hypoxia and down-regulated after shifting to reoxygenation. Although, it had well known that NDRG1 played a critical role in tumor adaptation to the fluctuation of oxygen concentrations, the regulatory mechanism of NDRG1 remained elusive.
In order to investigate the regulatory mechanism, we focused on the regulation between microRNAs (miRNAs) and NDRG1. In this study, breast cancer MCF-7 cells were cultured under 0.5% oxygen for 24 h followed by 24 h of reoxygenation. Cells were harvested at 0, 1, 12, and 24 h during reoxygenation, and examined the miRNA profile by Nanostring nCounter. Forty-three miRNAs had dramatic changes as compared with 0 h upon reoxygenation, with 63% (n=27) of the miRNAs up-regulated upon reoxygenation. In silico analysis revealed that, four miRNAs could perfectly match with 3'UTR sequences of NDRG1. Especially, miR-769-3p decreased the luciferase activity in the greatest extent and led a significant reduction of NDRG1 protein and mRNA upon reoxygenation. The role of miR-769-3p was investigated by over-expressing miR-769-3p in MCF-7 cells. Upon reoxygenation, miR-769-3p significantly inhibited cell proliferation and induced apoptosis. Our results were the first to reveal that NDRG1 could be regulated by miRNAs, and investigate the functions of miR-769-3p. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T08:28:34Z (GMT). No. of bitstreams: 1 ntu-102-R00441002-1.pdf: 1026103 bytes, checksum: 6ee18ac2c23556edd340b79abeb85a83 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 口試委員審定書 i
致謝 ii 中文摘要 iv Abstract v Chapter 1 Introduction 1 Hypoxia and reoxygenation in solid tumor 1 Relationship between NDRG1 and reoxygenation 2 MicroRNA and miR-769-3p 3 The aim of study 5 Chapter 2 Materials and Methods 7 Cell culture 7 Nanostring data analysis 7 Luciferase reporter assay 9 Site-directed mutagenesis 10 RNA extraction, reverse transcription, and quantitative RT-PCR 11 Western blot 13 MTT assay 13 Flow cytometry analysis of cell cycle and cell death 14 Chapter 3 Results 15 Down-regulation of NDRG1 under reoxygenation 15 Identification of miRNAs responsive to reoxygenation 16 In silico analysis of miRNAs binding sites in the 3'UTR of NDRG1 19 MiRNAs up-regulated under reoxygenation 20 NDRG1 is the target of miR-769-3p 22 The differential synthesis of miR-769-3p during oxygen fluctuation 24 Successful over-expression of miR-769-3p 26 Down-regulation of NDRG1 was enhanced by over-expressing miR-769-3p 27 Over-expression of miR-769-3p efficiently suppresses cell proliferation 28 Mir-769-3p induces apoptosis in MCF-7 29 Chapter 4 Discussion 33 The regulation of NDRG1 upon oxygen fluctuation 33 Data analysis of genome-wide microRNA using Nanostring 34 MiR-769-3p was chosen for further experiments 35 MiR-769-3p down-regulated NDRG1 upon reoxygenation but not hypoxia 36 MiR-769-3p enhanced apoptosis and inhibited cell proliferation 37 References 39 Appendix 48 | |
| dc.language.iso | en | |
| dc.subject | 缺氧 | zh_TW |
| dc.subject | 覆氧 | zh_TW |
| dc.subject | 微小RNA | zh_TW |
| dc.subject | NDRG1 | zh_TW |
| dc.subject | miR-769-3 | zh_TW |
| dc.subject | miR-769-3p | en |
| dc.subject | Reoxygenation | en |
| dc.subject | microRNA | en |
| dc.subject | NDRG1 | en |
| dc.subject | Hypoxia | en |
| dc.title | MicroRNA-769-3p於覆氧狀況下調降MCF-7細胞株中NDRG1基因表現並促進細胞凋亡 | zh_TW |
| dc.title | MicroRNA-769-3p Down-regulated NDRG1 and Enhanced Apoptosis in MCF-7 During Reoxygenation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 莊曜宇(Eric Yao-Yu Chuang),蔡孟勳(Mong-Hsun Tsai),佘玉萍(Yuh-Pyng Sher) | |
| dc.subject.keyword | 缺氧,覆氧,微小RNA,NDRG1,miR-769-3, | zh_TW |
| dc.subject.keyword | Hypoxia,Reoxygenation,microRNA,NDRG1,miR-769-3p, | en |
| dc.relation.page | 48 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2014-01-14 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生理學研究所 | zh_TW |
| 顯示於系所單位： | 生理學科所 | |
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