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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 廖憶純(Yi-Chun Liao) | |
dc.contributor.author | Jun-Rong Su | en |
dc.contributor.author | 蘇俊融 | zh_TW |
dc.date.accessioned | 2021-05-19T17:46:12Z | - |
dc.date.available | 2023-07-26 | |
dc.date.available | 2021-05-19T17:46:12Z | - |
dc.date.copyright | 2018-07-26 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-07-25 | |
dc.identifier.citation | 李家偉 (2008),室內鄰苯二甲酸酯類暴露與兒童健康之相關性--子計畫 四:室內含鄰苯二甲酸酯類之民生消費品逸散特性及影響因子之研究,行政院國家科學委員會專題研究計畫。
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7549 | - |
dc.description.abstract | 鄰苯二甲酸酯類 (phthalates or phthalate esters) 為一種廣泛使用的塑化劑,容易被釋放至環境中,透過呼吸系統或飲食過程,直接被攝取而危害消化系統。Phthalate 亦為內分泌干擾物質,關於其暴露所造成之健康危害,大多著重在研究乳癌、前列腺癌、生殖毒性及兒童發育方面的影響,對於大腸直腸癌方面的研究較少,因此,闡明鄰苯二甲酸酯類對大腸直腸癌腫瘤生成的影響與機制為當務之急。本論文藉由巨量生物資料庫,同時分析與 phthalate 暴露及大腸直腸癌腫瘤生成之關鍵基因,並進一步使用大腸細胞株進行驗證,探討其可能之調控機制。本研究首先搜尋基因資料庫 ArrayExpress 與 Gene Expression Omnibus,分析臨床大腸癌原位、轉移及正常組織,和人類細胞暴露 phthalate 的基因表現數據,以線上平台 NetworkAnalyst 比對,找到差異表現基因 (differentially expressed genes; DEG),接著,以分子網絡之整合性軟體 Cytoscape,進一步將 NetworkAnalyst 所找到之 DEG 重新進行關係串聯及視覺化,找到同時與 phthalate 暴露及大腸直腸癌發生與進程高度相關的關鍵基因與調控路徑。預測的基因網絡結果顯示,phthalate 暴露可能會影響以血管內皮生長因子 (vascular endothelial growth factor A; VEGFA) 為首之調控基因網絡,本研究進一步以人類正常大腸細胞株 CCD841 及大腸癌非轉移細胞株 SW480,驗證 diethylhexyl phthalate (DEHP) 對此預測訊息傳導路徑之影響,以即時定量 PCR 檢測基因表現的結果發現,上游目標基因 VEGFA、PDGFRB、SRC 及 AKT1等,在二種細胞株中皆如同預期在 DEHP 處理下有表現量上升的情況;而在 CCD841 中,下游目標基因 CDKN1A (p21) 及 CDKN1B (p27) 的表現,會隨著 DEHP 濃度的上升而逐漸提高,但在 SW480 中則沒顯著差異。另一方面,低濃度 DEHP (102 nM) 會使 SW480 細胞增生能力上升 1.2 倍,而高濃度 DEHP 則會抑制 CCD841 及 SW480 細胞增生的能力,高濃度 DEHP (106 nM) 還會使 CCD841 細胞移動能力增加 1.3 倍,但卻抑制 SW480 細胞移動能力。綜合本研究之結果顯示,DEHP 單獨暴露可能不會直接影響大腸細胞腫瘤發生以及加劇大腸直腸癌的進程。 | zh_TW |
dc.description.abstract | Phthalate or phthalate esters (PAEs) are widely used as plasticizers, which can be easily released into the environment. Phthalate can be directly absorbed through respiratory or digestive system. Phthalates are also endocrine-disrupting component and several studies regarding the effects of phthalate exposure are mainly focused on breast cancer, prostate cancer, reproductive toxicity and child development. However, the health effects of phthalate exposure on colorectal cancer are rarely discussed. Therefore, it is urgently needed to clarify the effect and mechanism of phthalates on colorectal tumorigenesis. In this study, emerging high-throughput omics technology is used to analyze the critical hub genes associated with phthalate exposure and colorectal tumorigenesis. The role of the critical hub genes in the predicted regulatory pathway are further validated using CRC cell lines exposed to phthalate. First, we analyze the gene expression database and compare the gene expressions of clinical primary CRC (pCRC), metastatic CRC (mCRC), normal colon tissues and human cells with phthalate exposure from ArrayExpress and Gene Expression Omnibus. Then NetworkAnalyst is used to determine the differentially expressed genes (DEG) in phthalate exposure (phthalate exposure vs. non-exposure), pCRC (primary CRC vs. normal colon) and mCRC (metastatic CRC vs. primary CRC). Furthermore, we establish and visualize the potential network to identify the potential hub genes and regulatory pathways associated with phthalate exposure in CRC by Cytoscape. The gene network shows that phthalate exposure may affect the vascular endothelial growth factor A (VEGFA)- mediated regulatory pathways. We next verify the predicted potential regulatory pathways using normal colon cell line CCD841 and non-metastasis colon cancer cell line SW480 treated with diethylhexyl phthalate (DEHP). Real-time PCR reveals that upstream regulatory genes, VEGFA, PDGFRB, SRC and AKT1, are up-regulated in the both cell lines. DEHP induces the expression of downstream regulatory genes, CDKN1A (p21) and CDKN1B (p27) in CCD841 cells whereas there is no difference in SW480 cells. On the other hand, the low dose (102 nM) of DEHP enhances 1.2-fold proliferative ability in SW480 cells and high dose (106 nM) of DEHP inhibits the proliferation in both cell lines. Treatment of 106 nM DEHP results in a 1.3-fold increase but decreases in cell migration in CCD841 and SW480 cells, respectively. To sum up, this study suggests that DEHP alone may not directly affect colorectal tumorigenesis and CRC progression. | en |
dc.description.provenance | Made available in DSpace on 2021-05-19T17:46:12Z (GMT). No. of bitstreams: 1 ntu-107-R05b22045-1.pdf: 3090500 bytes, checksum: 9a480dce94e3a5142cc2103fc2e60856 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 目錄
目錄 i 縮寫表 iii 中文摘要 vi Abstract viii 1. 研究背景 1 1.1 鄰苯二甲酸酯類 1 1.2 鄰苯二甲酸酯類在台灣之流布狀況 1 1.3 台灣塑化劑事件及後續追蹤研究 2 1.4 鄰苯二甲酸酯類之癌細胞特性相關實驗 2 1.6 大腸直腸癌之流行病學 4 1.7 大腸直腸癌發展進程分期 5 1.8 大腸直腸癌致癌機制 6 1.9 本論文之研究目的及重要性 7 2. 材料與方法 9 2.1 細胞製備 9 2.1.1 細胞株 9 2.1.2 藥品 9 2.1.3 細胞培養液 9 2.1.4 細胞培養 9 2.1.5 繼代培養 10 2.1.6 細胞冷凍保存與解凍細胞 10 2.1.7 細胞計數 11 2.2 資料庫蒐集及分析 11 2.2.1 蒐集微陣列資料庫 11 2.2.2 鄰苯二甲酸酯類暴露之微陣列資料庫之前處理 12 2.2.3 差異表現基因之分析及基因模組之建立 12 2.2.4 基因網絡之功能及網絡間之交互作用 13 2.2.5 基因本體 (Ontology) 分析 13 2.3 細胞模式實驗 14 2.3.1 細胞增生分析 14 2.3.2 細胞移動分析 14 2.3.3 RNA 萃取 15 2.3.4 反轉錄製備 cDNA (complementary DNA) 16 2.3.5 定量聚合酶連鎖反應 (quantitative polymerase chain reaction, qPCR) 16 3. 研究結果 17 3.1 鄰苯二甲酸酯類暴露和大腸直腸癌進程之模組基因之基因本體分析 (Ontological analysis) 17 3.2 鄰苯二甲酸酯類暴露和大腸直腸癌進程之模組基因之基因調節網絡 18 3.3 鄰苯二甲酸酯類暴露可能誘發大腸癌腫瘤發生及加速癌化進程相關之潛在調節路徑 19 3.4 鄰苯二甲酸酯類暴露及大腸癌化進程之差異表現基因之 GO terms 20 3.5 DEHP 暴露影響預測之目標基因表現量變化 21 3.6 DEHP 毒性測試及對於人類大腸細胞增生之影響 22 3.7 DEHP 暴露對於人類大腸細胞移動之影響 23 3.8 Lipopolysaccharide (LPS) 與 DEHP 共同暴露對於細胞移動、預測之目標基因及發炎相關因子之影響 23 4. 討論 25 4.1 DEHP 暴露對於分析微陣列資料庫之差異表現基因於大腸細胞 CCD841 及大腸癌細胞 SW480之影響 25 4.2 DEHP 暴露對於大腸細胞 CCD841 及大腸癌細胞 SW480 細胞增生能力之影響 26 4.3 DEHP 暴露對於大腸細胞 CCD841 及大腸癌細胞 SW480細胞移動能力之影響 28 4.4 DEHP 暴露對於大腸細胞 CCD841 及大腸癌細胞 SW480 是否有誘導癌化之可能 28 4.5 LPS 與 DEHP 共同暴露對於大腸細胞 CCD841 之影響 30 4.6 DEHP 之代謝產物 MEHP 暴露對於癌化特性之影響 31 5. 結論 32 6. 參考資料 33 7. 圖和表 45 | |
dc.language.iso | zh-TW | |
dc.title | 探討鄰苯二甲酸酯類影響大腸直腸癌腫瘤生成之相關基因網絡 | zh_TW |
dc.title | Study on the potential gene network associated with phthalate exposure and tumorigenesis in colorectal cancer cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 莊淳宇(Chun-Yu Chuang),賴韻如(Yun-Ju Lai),謝淑貞(Shu-Chen Hsieh) | |
dc.subject.keyword | 大腸直腸癌,鄰苯二甲酸酯類,巨量生物資料庫,ArrayExpress,NetworkAnalyst,差異表現基因,Cytoscape,調控路徑,血管內皮生長因子, | zh_TW |
dc.subject.keyword | phthalates,colorectal cancer,meta-biological database,ArrayExpress,NetworkAnalyst,differentially expressed gene,Cytoscape,regulatory pathway,vascular endothelial growth factor, | en |
dc.relation.page | 67 | |
dc.identifier.doi | 10.6342/NTU201801933 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2018-07-25 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科技學系 | zh_TW |
dc.date.embargo-lift | 2023-07-26 | - |
顯示於系所單位: | 生化科技學系 |
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