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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 | 李明學 | |
dc.contributor.author | Yi-Chin Lin | en |
dc.contributor.author | 林苡勤 | zh_TW |
dc.date.accessioned | 2021-06-17T08:07:17Z | - |
dc.date.available | 2024-08-27 | |
dc.date.copyright | 2019-08-27 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-08-19 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73642 | - |
dc.description.abstract | 大腸直腸癌是現今世界各地常見的癌症,其癌症致死率高居第三名。在台灣,國人的大腸直腸癌發生率在十大癌症中排名第三名。雖然目前在大腸直腸癌的治療上已有許多突破,但在對於癌症發生轉移的病人身上,其死亡率仍是高居不下,五年存活率僅有一成。近年來的研究發現,甲基化修飾和大腸直腸癌疾病的進程有密切的關係。在本篇研究中,我探討精胺酸甲基轉移酶和大腸直腸癌惡化的關係。根據公開的資料庫,透過生物資訊的分析和統計,發現精胺酸甲基轉移酶2、精胺酸甲基轉移酶3、精胺酸甲基轉移酶5的基因表達量和大腸直腸癌病人的存活率有著高度的相關性。在這三個基因中,更進一步發現精胺酸甲基轉移酶3的基因表達量隨著癌症越惡化,其基因表現量也隨著下降。此外,在細胞實驗中也發現,當精胺酸甲基轉移酶3的表現量下降時,大腸直腸癌細胞的細胞移動能力增強,接著發現,絲胺酸蛋白酶抑制劑可以抑制精胺酸甲基轉移酶3基因低表現的癌細胞的侵襲能力。並進一步用人類蛋白質水解酵素晶片來分析,發現精胺酸甲基轉移酶3低表現的細胞中激肽釋放酶5的表現量顯著的上升。總結來說,精胺酸甲基轉移酶3在大腸直腸癌發展的過程中,透過調控激肽釋放酶5此酵素,扮演抑制癌症惡化的角色。 | zh_TW |
dc.description.abstract | Colorectal cancer is one of the most common cancers and the third leading cause of cancer-related mortality in Taiwan and worldwide. Although cancer therapies have been improved, the mortality of metastatic colorectal cancer patients still remains high. The epigenetic modification of methylation has been proposed to be involved in colorectal cancer development and progression and arginine methylation is a newly identified mechanism for post translation modification. In this study, I analyzed if there was an alteration of a protein arginine methyltransferase (PRMT) in human colorectal cancer. According to a public database, the bioinformatics analysis showed that the alterations of the PRMT2, PRMT3 and PRMT5 gene expression levels were correlated with the survival rates of colorectal cancer patients. Among these three genes, I further found that the expression levels of PRMT3 were decreased in the colorectal cancer cells isolated from Dukes’ D, compared to those cells from Dukes’ B and C. Moreover, PRMT3 silencing increased colorectal DLD-1 and HCT116 cancer cell invasion. The PRMT3 knockdown-induced colorectal cancer cell invasion was able to be inhibited by a broad serine protease inhibitor, suggesting a serine protease is involved in PRMT3 signaling of colorectal cancer cells. Moreover, I used a protease array analysis and found that the expression levels of kallikrein 5 were dramatically increased in PRMT3 silencing colorectal cancer cells. The results together indicate that PRMT3 plays a suppression role in colorectal cancer cell invasion and kallikerin 5 may be involved in PRMT3-mediated colorectal cancer progression. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T08:07:17Z (GMT). No. of bitstreams: 1 ntu-108-R06442005-1.pdf: 2165967 bytes, checksum: fda93a5010e03dd16e5373a1038e5522 (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | Content
Chapter 1. Introduction 1 1.1 Colorectal cancer 2 1.2 Arginine methylation 4 1.3 Protein arginine methyltransferases (PRMTs) 5 1.4 Protein arginine methyltransferases 3 (PRMT3) 6 1.5 The purpose of this study 7 Chapter 2. Materials and Methods 9 Chapter 3. Results 19 3.1 Inverse correlation between PRMT3 expression with colorectal cancer progression and poor prognosis. 20 3.2 A decreased protein level of PRMT3 in a colorectal cancer cell progression model. 21 3.3 PRMT3 played an inhibitory role in colorectal cancer cell migration and invasion 22 3.4 Involvement of serine proteases in PRMT3 knockdown-induced colorectal cancer cell motility. 22 3.5 Increased gelatinolytic activity of MMP2 in PRMT3-knockdowned DLD-1 cells. 23 3.6 Up-regulation of Kallikrein5 expression levels in PRMT3-knockdowned HCT116 cells using protease array profiling 23 Chapter 4. Figures 25 Figure 1. Correlation of PRMTs expression with colorectal cancer patient survival and poor prognosis. 27 Figure 2. Examination of PRMT3 expression in different colorectal cancer cells. 29 Figure 3. PRMT3 silencing increased colorectal cancer cell migration and invasion. 31 Figure 4. Effects of serine protease and metelloprotease inhibitors on PRMT3-knockdown-induced colorectal cancer cell invasion. 32 Figure 5. Analysis of the gelatinolytic activity in the conditioned media of PRMT3-knockdown DLD-1 cells. 34 Figure 6. Protease profiling analysis of the protease protein levels in PRMT3-knockdown HCT116 cells using protease array profiling. 37 Chapter 5. Discussion 39 Chapter 6. References 44 | |
dc.language.iso | en | |
dc.title | 甲基轉移酶PRMT3在大腸癌細胞惡化及侵襲移動能力中所扮演的角色 | zh_TW |
dc.title | Role of protein arginine methyltransferase 3 in colorectal cancer cell invasion and progression | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 張富雄 | |
dc.contributor.oralexamcommittee | 華國泰,張震東,黃祥博 | |
dc.subject.keyword | 大腸直腸癌,精胺酸甲基轉移?3,侵襲能力,激?釋放?5,甲基化修飾, | zh_TW |
dc.subject.keyword | Colorectal cancer,PRMT3,Cell invasion,KLK5,methylation, | en |
dc.relation.page | 48 | |
dc.identifier.doi | 10.6342/NTU201903979 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-08-19 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
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