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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 阮雪芬 | |
dc.contributor.author | Cheng-Pao Chen | en |
dc.contributor.author | 陳正寶 | zh_TW |
dc.date.accessioned | 2021-06-13T00:38:05Z | - |
dc.date.available | 2012-07-30 | |
dc.date.copyright | 2007-07-30 | |
dc.date.issued | 2007 | |
dc.date.submitted | 2007-07-25 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29068 | - |
dc.description.abstract | 全反式維甲酸(all-trans retinoic acid, ATRA)與Am80是用於治療血癌,促使血癌細胞HL-60分化成顆粒球已經有很多年了,其中全反式維甲酸是天然的維他命A類似物,Am80則是經過合成改良的藥物,這兩種藥物對於誘導HL-60分化都有不錯的效果。在本篇的研究,我們利用基因微陣列晶片與生物資訊軟體的方法來挑選出在細胞分化中基因表現量上有差異的基因。軟體統計分析的結果顯示TGF-β訊號傳遞的生物路徑是ㄧ個被誘導出的生物路徑,就我們所知的,TGF-β訊號傳遞的生物路徑是ㄧ個與調控細胞分化、細胞增生有關的生物路徑,我們利用偵測與這個生物路徑有關的時間序列上的基因表現,來建構一個可能被ATRA與Am80所誘導的基因網路,再利用MiLINK這個軟體來找到這個可能與這個生物路徑有關的微型核醣核酸,這些微型核醣核酸可能扮演調控這個基因網路的角色,那微型核醣核酸他們主要是存在於非產生蛋白質的序列上,並且是單股約20~25個核甘酸的長度,他們被報導出具有調控細胞生長、細胞分化、還有一些疾病和癌症的產生有關,到現在為止,在人類基因組中已經有超過三百個微型核醣核酸被發現,在我們的結果中,miR-96與miR-107的表現都有顯著得被兩種藥物給誘導表現,這個結果告訴我們這個miR-96與miR-107可能是參與調控細胞分化的重要因子。 | zh_TW |
dc.description.abstract | All-trans retinoic acid (ATRA) and Am80, natural and synthetic derivatives of Vitamin A, have been used in oncology for many years and are useful for inducing HL-60 to differentiate to granulocyte. In this study, we showed that TGF-β signaling pathway is the most perturbed and involved in differentiation process using microarray and bioinformatics approach. With time-series gene expression profiles measured by the quantitative real-time PCR, we constructed a gene network of ATRA- and Am80-induced human leukemia cell line HL-60 differentiation. The results from comparative analysis of target genes indicated that this gene network was regulated by some candidate microRNAs. MicroRNAs are non-coding, single-stranded RNAs of 20 ~ 25 nucloetides that execute a gene regulator function responsible for cell growth, cell differentiation, disease, and cancer. In our results, the expression of miR-96 and miR-107 were significantly induced by ATRA and Am80. In summary, our results showed that miR-96 and miR-107 seem to be the regulators involved in the gene network of leukemia cell differentiation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T00:38:05Z (GMT). No. of bitstreams: 1 ntu-96-R94b43016-1.pdf: 4579283 bytes, checksum: 78c2e875851460826d13adf1b2371bca (MD5) Previous issue date: 2007 | en |
dc.description.tableofcontents | 口試委員會審定書 I
誌謝 II 中文摘要 IV Abstract V 第一章 前言 1 1.1 血癌 1 1.1.1血癌( Leukemia )簡介 1 1.1.2 慢性淋巴型血癌( Chronic Lymphocytic Leukemia ) 2 1.1.3 急性淋巴型血癌( Acute Lymphocytic Leukemia ) 2 1.1.4 慢性骨髓型血癌( Chronic Myeloid Leukemia ) 3 1.1.5 急性骨髓型血癌( Acute Myeloid Leukemia ) 4 1.1.6 急性原骨髓型血癌(Acute Promyelocytic Leukemia)細胞HL-60 5 1.2 All-trans retinoid acid & Am80藥物介紹與影響 9 1.2.1 ATRA ( All-trans retinoic acid )藥物介紹 9 1.2.2 Am80藥物介紹 10 1.2.3 ATRA & Am80對於細胞分化的分子機制 10 1.2.4 ATRA & Am80藥物的副作用 12 1.3 TGF-β訊號生物路徑 12 1.4 微型核醣核酸MicroRNA 14 1.4.1 miRNA的介紹 14 1.4.2 miRNA的生成路徑 15 1.4.3 miRNA對於基因的調控方式 16 1.4.4 miRNA與siRNA的差異 16 1.4.5 miRNA對於細胞的影響 17 第二章 實驗材料與方法 19 2.1 實驗流程 19 2.2 細胞培養 20 2.3 細胞染色 24 2.4 萃取總RNA (分基因表現偵測使用與微型核醣核酸表現偵測使用兩部份) 26 2.4.1 基因表現偵測使用 26 2.4.2 微型核醣核酸表現偵測使用 28 2.5 cDNA製備 (分基因表現偵測使用與微型核醣核酸表現偵測使用兩部份) 30 2.5.1 基因表現偵測使用 30 2.5.2 微型核醣核酸表現偵測使用 32 2.6 即時偵測聚合酶連鎖反應引子設計 33 2.7 即時偵測聚合酶連鎖反應基因表現量與微型核醣核酸表現量偵測 34 2.7.1 基因表現量偵測 34 2.7.2 微型核醣核酸表現量偵測 39 2.8 生物資訊軟體分析 40 2.8.1. GeneSpring –microarray資料分析軟體 40 2.8.2 MeV –生物晶片資料視覺化軟體分析 41 2.8.3 ArrayXPath –生物路徑軟體分析 41 2.8.4 BSIP –基因網路建構軟體 43 2.8.5 MiLink-目標基因與對應目標微型核醣核酸連結 44 第三章 結果 47 3.1藥物誘導促使細胞分化所造成外型的變化 47 3.2藥物對於HL-60血癌細胞分化基因的影響 47 3.3在血癌細胞中,藥物對於生物路徑的影響 48 3.4藥物誘導TGF-β訊號生物路徑中基因的表現 49 3.4.1即時定量聚合酶連鎖反應偵測基因表現量結果 49 3.4.2 Two-way ANOVA與T-test統計分析基因表現之顯著性 50 3.4.3即時定量聚合酶連鎖反應與生物微陣列晶片偵測表現量之比較 51 3.5藥物所誘導基因網路 52 3.6基因與微型核醣核酸的關係 53 3.7藥物誘發的微型核醣核酸表現 53 3.7.1即時定量聚合酶連鎖反應偵測微型核醣核酸表現量結果 53 3.7.2 Two-way ANOVA與T-test統計分析微型核醣核酸表現之顯著性 54 3.8微型核醣核酸對於TGF-β訊號生物路徑中基因表現量的比較 55 第四章 討論 57 4.1藥物處理下,骨髓型細胞分化相關基因的表現 57 4.2 TGF-β訊號生物路徑與顆粒球細胞分化的關係 58 4.2.1 藥物ATRA與Am80處理後,基因表現量變化與時間點變化之關係 58 4.2.2 即時定量聚合酶連鎖反應與生物微陣列晶片偵測值之比較 59 4.2.3 藥物ATRA與藥物Am80所誘導的基因網路 60 4.3微型核醣核酸對於顆粒球細胞分化的影響 61 4.3.1 藥物所誘導的微型核醣核酸的表現 61 4.3.2 miR-96與SMAD1、SMAD7調控的關係 62 4.3.3 miR-107與SMAD7調控的關係 63 4.3.4 微型核醣核酸與調控的基因網路 63 第五章 未來展望 65 實驗結果 (圖) 66 實驗結果 (表) 102 參考文獻 118 附錄 130 | |
dc.language.iso | zh-TW | |
dc.title | ATRA與Am80誘導HL-60分化的調控機制:微型核醣核酸與基因網路 | zh_TW |
dc.title | The regulatory mechanism of ATRA- and Am80-induced HL-60 cell differentiation: miRNA and gene network | en |
dc.type | Thesis | |
dc.date.schoolyear | 95-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃宣誠,陳水田 | |
dc.subject.keyword | ATRA,Am80,HL-60,血癌,基因網路,微型核醣核酸, | zh_TW |
dc.subject.keyword | ATRA,Am80,HL-60,Leukemia,Gene network,miRNA, | en |
dc.relation.page | 155 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2007-07-25 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
顯示於系所單位: | 分子與細胞生物學研究所 |
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