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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 | 楊泮池(Pan-Chyr Yang) | |
dc.contributor.author | Ching-Wen Lin | en |
dc.contributor.author | 林晴雯 | zh_TW |
dc.date.accessioned | 2021-06-16T16:05:33Z | - |
dc.date.available | 2014-09-24 | |
dc.date.copyright | 2013-09-24 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-06-20 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/62610 | - |
dc.description.abstract | 肺癌(主要為非小細胞肺癌)是國人及世界上因癌症造成死亡的主要原因之一。其治療以及診斷上仍有許多困難及障礙,故深入瞭解造成肺癌病變以及轉移的特殊分子機制有助新療法的發展。微核糖核酸(miRNAs) 是小片段且非編碼(non-coding)的單股內生性RNA,藉由類似RNAi的方式抑制並調控下游基因的轉錄進而影響細胞增生、發育以及凋亡。近期研究發現特定微核糖核酸能作為抑癌基因或是致癌基因,因其表現量的改變會間接造成下游基因群的表現變異,使得細胞產生病變進而惡性癌化。
利用miRNAs微陣列晶片,我們發現微核糖核酸-135b (miR-135b)的表現與癌症細胞轉移能力高度相關,且其在非小細胞肺癌病人中的表現量與病人存活率成反比。大量表現miR-135b 會促進肺癌細胞的移動以及侵犯能力;若抑制miR-135b則能降低肺癌細胞的移動以及侵犯能力。動物實驗顯示miR-135b抑制劑(antagomiR以及sponge )對於肺癌細胞的轉移則具有抑制的效果。以報導基因分析法以及蛋白質轉漬實驗顯示抑癌基因LZTS1以及 Hippo pathway 部分成員是miR-135b所調控的標的基因群。而LZTS1, LATS2在肺腺癌病人中的表現量與病人的存活率成正比; 而細胞核內的TAZ之表現量則與存活率成反比。 我們也發現miR-135b的表現同時受到其啟動子 的甲基化程度以及轉錄因子 NF-kB的調控。顯示miR-135b在癌細胞中的不正常表現可能同時來自於微環境中的免疫機制以及表基因機制(epigenetic mechanism)的變異所影響。綜合以上的結果,我們認為miR-135b為致癌基因, 而其抑制劑具有治療非小細胞癌的潛力。 | zh_TW |
dc.description.abstract | Dysregulation of microRNAs (miRNAs) plays a critical role in cancer progression. In this study, we identified an intronic miRNA, miR-135b, that is upregulated in highly invasive non-small-cell lung cancer (NSCLC) cells. Expression of miR-135b enhanced cancer cell invasive and migratory abilities in vitro and promoted cancer metastasis in vivo, whereas specific inhibition of miR-135b by miR-135b-specific molecular sponge and antagomirs suppressed cancer cell invasion, orthotopic lung tumor growth and metastasis in mouse model. The miR-135b targets multiple key components in the Hippo pathway, including LATS2, β-TrCP, and NDR2, as well as the LZTS1. Expression of miR-135b, LZTS1, LATS2, and nuclear TAZ predicted poor outcomes of NSCLC. We found that miR-135b was regulated by DNA both de-methylation and NF-κB signaling, implying that abnormal expression of miR-135b in cancer may be resulted from inflammatory and epigenetic modulations. We concluded that miR-135b is an oncogenic miRNA and a potential therapeutic target for NSCLC. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T16:05:33Z (GMT). No. of bitstreams: 1 ntu-102-D96448002-1.pdf: 6236037 bytes, checksum: 7c7daf41967f84af3a5c34196fd87583 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 中文摘要 4
Abstract 5 CHAPTER 1: General Introduction 11 1.1 Lung cancers metastasis 12 1.2 The regulation of microRNAs 13 1.3 miR-135b 14 CHAPTER 2: Identification of the Functions of miR-135b in Lung Cancers 17 2.1 Introduction 18 2.2 Motivation and Hypothesis 20 2.3 Material and Methods 21 2.4 Results 32 2.5 Discussion 48 CHAPTER 3: Identification of the Regulatory Mechanism on the Expression of miR-135b……………………………………………………………………………………....52 3.1 Introduction 53 3.2 Motivations and Purpose 55 3.3 Materials and Methods 56 3.4 Results 62 3.5 Discussion 66 CHAPTER 4 : 69 Conclusion 69 References 71 | |
dc.language.iso | en | |
dc.title | 探討miR-135b在肺癌中的分子調控機制 | zh_TW |
dc.title | MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1 | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 洪澤民,吳君泰,陳健尉,徐立中 | |
dc.subject.keyword | 微核糖核酸-135b,LZTS1,LATS2,TAZ,非小細胞癌,癌轉移,存活率,微核糖核酸,antagomiR, | zh_TW |
dc.subject.keyword | miR-135b,LZTS1,LATS2,TAZ,NSCLC,Metastasis,Survival,miRNA,antagomiR, | en |
dc.relation.page | 129 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-06-20 | |
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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