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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳青周(Ching-Chow Chen) | |
| dc.contributor.author | Ping Luo | en |
| dc.contributor.author | 羅平 | zh_TW |
| dc.date.accessioned | 2021-06-15T11:32:33Z | - |
| dc.date.available | 2016-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-17 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49517 | - |
| dc.description.abstract | HMGCR (3-Hydroxy-3-methyl-glutaryl-CoA reductase, HMGCR)是合成膽固醇的速率決定酵素，將 HMG-CoA轉換成mevalonate，因此膽固醇生合成路徑也稱為mevalonate pathway；活化mevalonate pathway會促進GTPase farnesylation，加速細胞之生長與癌化；臨床上，服用Statins (HMGCR 抑制劑)可減少血中膽固醇濃度，降低心血管與腦血管疾病之發生率。大腸直腸癌(Colorectal Cancer, CRC)為世界發生率第三高之癌症，其患者腫瘤組織之HMGCR活性較正常組織高，服用statins可降低罹患大腸直腸癌之風險，我們使用HMGCR表現較多的HCT116以及HMGCR表現較低的SW480來探討HMGCR在大腸直腸癌的角色。
使用shRNA knockdown或CRISPR knockout HCT116之HMGCR，會增加apoptotic marker (Cleaved caspase-3)之表現，減少pro-survival (Mcl-1)之表現；Overexpress HMGCR至SW480則增加Mcl-1之表現，與發炎相關的COX-2以及引發DNA de novo methylation的DNMT3A之表現亦增加，推論HMGCR是CRC致癌因子之一。 我們以RNA sequencing分析兩組TKI-resistant 細胞，HCC827 vs HCC827/IR和H1975 vs H1975/AR，發現參與調控cell adhesion、tight junction以及提升cell migration能力之蛋白之mRNA有差異，例如cell adhesion相關的E-cadherin與Occludin之表現量在HCC827/IR和H1975/AR較少；另外，我們分析lncRNAs表現之差異，發現兩個lncRNAs：CLU及CRNDE高度表現在HCC827/IR和H1975/AR細胞，主要分布在核內，使用DNA gapmers knockdown CLU與CRNDE，探討其在TKI-resistance的角色。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-15T11:32:33Z (GMT). No. of bitstreams: 1 ntu-105-R03443014-1.pdf: 8702664 bytes, checksum: afaaa46e06ef4d4dc52a5aa221b8b651 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 縮寫表…………………………………………………………………………………2
中文摘要………………………………………………………………………………5 英文摘要………………………………………………………………………………6 第一章 緒論……………………………………………………………………….…..7 第一節 Hydroxymethylglutaryl coenzyme A reductase (HMGCR)……8 第二節 大腸直腸癌 (Colorectal cancer)…………..…………………………..16 第三節 Cancer Stem Cell…………..………………………………………….…..25 第四節 Long Non-coding RNA in Cancer………………………………….…….33 第五節 研究動機………………………………………………………………….43 第二章 實驗材料與方法……………………………………………………………44 第三章 結果………………………………………………………………………....53 第四章 討論…………………………………………………………………………67 第五章 結論…………………………………………………………………………70 參考文獻……………………………………………………………………………..72 | |
| dc.language.iso | zh-TW | |
| dc.title | HMGCR在大腸直腸癌之角色以及lncRNA在肺癌TKI抗藥性之研究 | zh_TW |
| dc.title | The role of HMGCR in colorectal cancer and the study of lncRNA in lung cancer TKI-resistance | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳明賢(Ming-Shiang Wu),黃偉謙(Wei-Chien Huang),楊鎧鍵(Kai-Chien Yang) | |
| dc.subject.keyword | HMGCR,大腸直腸癌,TKI,tyrosine kinase inhibitor,非小細胞肺癌,lncRNA, | zh_TW |
| dc.subject.keyword | HMGCR,Colorectal cancer,TKI,tyrosine kinase inhibitor,non-small cell lung cancer,lncRNA, | en |
| dc.relation.page | 84 | |
| dc.identifier.doi | 10.6342/NTU201602990 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-17 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥理學研究所 | zh_TW |
| 顯示於系所單位： | 藥理學科所 | |
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