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研究生:廖皓涵
研究生(外文):Hao-Han Liaw
論文名稱:乳癌中選擇性多腺苷酸化模式與微型核糖核酸調控之關聯研究
論文名稱(外文):MicroRNA Modulation of Alternative Polyadenylation Pattern in Breast Cancer Cells
指導教授:黃宣誠
指導教授(外文):Hsuan-Cheng Huang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生物醫學資訊研究所
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:2012
畢業學年度:100
語文別:英文
論文頁數:45
中文關鍵詞:選擇性多腺苷酸化微型核糖核酸乳癌
外文關鍵詞:Alternative PolyadenylationMicroRNABreast Cancer
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選擇性多腺苷酸化可造成同一基因產生不同3’ UTR長度的mRNA,其中長度較短的mRNA型態可能因此失去被某些microRNA調控的區域,而與長度較長的mRNA型態承受不同程度的調控。前人研究指出在癌細胞中,基因大致上都傾向於表現長度較短的mRNA型態。為了瞭解microRNA調控與長短型態mRNA比例的關係,我們從公開的乳癌細胞研究數據中,收集並分析各個基因的選擇性多腺苷酸化註解、長短型態mRNA表現量以及各種microRNA的表現量資訊。首先,我們發現microRNA在長型mRNA才有的3’ UTR區域 (aUTR)中所調控的位置數目,會影響其目標基因的長短mRNA比例。接著,我們觀察到在癌細胞中表現量上升的microRNA,其目標基因的長短mRNA比例較正常細胞來的低,而且與表現量下降的microRNA相比,這些microRNA的調控位置傾向於出現在aUTR上。最後,我們也證實在癌細胞中表現上升的microRNA對aUTR的調控位置數目愈多,其目標基因在癌細胞中的長短mRNA比例相較於正常細胞中的比例為愈低。以上結果顯示,在癌細胞中表現量上升的microRNA應該會降解目標基因的長型mRNA而造成長短型態mRNA的比例下降。這個現象很可能是癌細胞中基因表現的整體長短mRNA比例偏低的一個重要促成因子。
Alternative polyadenylation (APA) could result in mRNA isoforms with variable length of 3’ UTRs. Gain of some microRNA target sites in 3’ UTR of a long mRNA isoform may cause different regulation from the corresponding short isoform. It has been known that cancer cells globally exhibit lower ratio of long and short isoforms (LSR), that is, they tend to express larger amount of short isoforms. To illustrate the relation between microRNA differential regulation and LSR, we analyzed published APA annotations, isoform expression and microRNA expression profiles of breast cancer and normal cells. Firstly, we found that the amount of microRNA target sites in alternative UTR (aUTR), the region only present in long isoforms, could affect LSR of the target genes. Secondly, we observed that the aUTR target genes of up-regulated microRNAs in tumor cells had overall lower LSR. Furthermore, the target sites of tumor-up-regulated microRNAs tended to appear in aUTR. Finally, we demonstrated that the amount of target sites of tumor-up-regulated microRNAs in aUTRs was correlated with the LSR change between cancer and normal cells. These results indicated that up-regulation of microRNAs might result in lower LSR of target genes in cancer cells through degradation of their long isoforms. This phenomenon can potentially contribute to the mechanism of global LSR decrease in cancer cells.
Contents
中文摘要.............................. i
Abstract.............................. iii
Contents.............................. v
List of Figures....................... vii
Chapter 1 : Introduction.............. 1
1.1 MicroRNA regulation............... 1
1.2 Alternative polyadenylation....... 2
Chapter 2 : Materials and Methods..... 6
2.1 APA annotation and mRNA isoform expression data... 6
2.2 MicroRNA expression profiles...... 7
2.3 MicroRNA target sites............. 7
2.4 Overall LSR of targets versus non-targets... 8
2.5 MicroRNA differential expression.. 10
2.6 LSR change of targets between cell types... 10
2.7 Target-site preference in aUTR.... 12
Chapter 3 : Results................... 13
3.1 Preference of APA genes for short isoforms in breast cancer cells... 13
3.2 MicroRNA target site versus LSR... 21
3.3 MicroRNA differential expression versus LSR change of targets... 25
3.4 Preference of microRNA target sites to appear in aUTRs... 28
3.5 Target sites of up-regulated microRNAs versus LSR change in MCF-7 Cells... 30
Chapter 4 : Discussion............... 34
Chapter 5 : Conclusion............... 40
Bibliography.......................... 41

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