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研究生:尤昭傑
研究生(外文):Jau-Jie You
論文名稱:尋找自然反義轉錄與癌症關係之驗證
論文名稱(外文):Natural antisense with human cancer
指導教授:許芳榮許芳榮引用關係王玲玲王玲玲引用關係
指導教授(外文):Fong-Rong HsuLing-Ling Wang
學位類別:碩士
校院名稱:亞洲大學
系所名稱:生物資訊研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2005
畢業學年度:94
語文別:英文
論文頁數:33
中文關鍵詞:自然反義轉錄表達序列標籤資料庫人類癌症專一性即時定量聚合脢連鎖反應
外文關鍵詞:Natural Antisense TranscriptsExpressed Sequence TagsDatabaseHumansCancer-SpecificReal-time Quantitative Polymerase Chain Reaction
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自然反義轉錄最早是在原核生物上發現,後來在高等生物上也証實有此現象。所謂反義轉錄是指轉錄子與對股有一段序列互補且會影響對股基因轉錄之行為。所謂自然是指它是天然內源性的。這種特殊轉錄子會藉由影響對股基因轉錄行為而直接進行基因調控;像是transcriptional interference,RNA masking,double-stranded RNA (dsRNA)-dependent mechanisms,genomic imprinting,alternative splicing,X-inactivation都與此有關。而在人類基因體上,預測有1到20百分比有此自然反義轉錄現象。
利用反義轉錄來做為藥物設計一直是一個熱門的話題,但自然反義轉錄是否參與癌變過程則仍未有文獻報告。我們利用表達序列標籤資料庫與人類癌症基因的註解,找出了6551對自然反義轉錄。並且利用即時定量聚合脢連鎖反應驗證其中3對。我們發現在人類腫瘤組織與正常組織確實存在這些基因對有表現量差異,証實自然反義轉錄現象在癌化過程有一定之角色。
Natural antisense transcripts (NATs) were first described in prokaryotes, and also were found in the eukaryotic cell later. The ‘antisense’ term includes transcripts containing long sequences complementary to sense transcripts, and the ‘nature’ term means endogenous. This transcriptome were found to regulate the expression of sense transcripts involved in diverse biological function, such as transcriptional interference, RNA masking, double-stranded RNA (dsRNA)-dependent mechanisms, genomic imprinting, alternative splicing, X-inactivation. In the human genome, it was predicted about 1% to 20% of the human genes were influenced by antisense transcripts.
The antisense had been widely used as drug design application. But there is no literature confirms the relationship between the tumorgenesis and NATs. Our laboratory had recently cluster the sense-antisense gene pairs, based on NCBI (National Center for Biotechnology information) expressed sequence tags source and NCI-CGAP (National Cancer Institute – Cancer Genome Anatomy Project) annotation. The dataset identify 6,551 NATs clusters. We random selected three NATs gene pairs and performed Q-PCR (real-time quantitative polymerase chain reaction) examination. The mRNA expression level of NATs shows different expression between human cancer and normal-tissue. It proved the reliable of our dataset and that the NATs do play a role in the tumorgenesis.
Table of Contents
Acknowledgement
中文摘要 .................................................i
Abstract ...............................................ii
Table of Contents .....................................iii
List of Tables ..........................................v
List of Figures.........................................vi
Chapter 1 Introduction ..........................................1
1.1 Motivation ..................................................1
1.2 Goal.........................................................2
Chapter 2 Background and Related work............................3
2.1 Natural antisense transcripts and its biological function....3
2.1.1 Background and discovery of NATs...........................3
2.1.2 NATs with transcriptional interference.....................4
2.1.3 NATs with RNA masking......................................4
2.1.4 NATs with dsRNA-dependent mechanisms.......................5
2.1.5 NATs with genomic imprinting and X-inactivation............5
2.1.6 NATs with alternative splicing.............................6
2.1.7 NATs with circadian clocks.................................7
2.1.8 NATs is not transcriptional leakage........................7
2.2 Recent biotechnology and bioinformatics approach for NATs....9
2.2.1 The systemic biotechnology approach........................9
2.2.2 The global bioinformatics approach.........................9
2.3 NATs with carcinogenesis or tumorgenesis....................13
Chapter 3 Material and Method...................................14
3.1 Data source.................................................14
3.1.1 Database source...........................................14
3.1.2 Candidate selection.......................................15
3.2 Q-PCR examination...........................................16
3.2.1 Material..................................................16
3.2.2 Method....................................................16
3.2.3 Statistics................................................17
Chapter 4 Results and Discussion................................18
4.1 Results.....................................................18
4.2 Discussion..................................................20
4.2.1 The NATs model of MYO7B and LIMS2.........................20
4.2.2 The NATs model of MED25 and RASD1.........................20
Chapter 5 Conclusion and future research........................22
References......................................................23
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