請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19197
標題: | 探討在神經母細胞瘤中長鏈非編碼核糖核酸和MYCN調控網路的交互作用 Identification of lncRNA-modulated MYCN Regulatory Networks in Neuroblastoma |
作者: | Yun-Peng Chen 陳允芃 |
指導教授: | 阮雪芬 |
關鍵字: | 神經母細胞瘤,lncRNA,MYCN,交互作用,調節角色, Neuroblastoma,lncRNA,MYCN,interaction,modulator, |
出版年 : | 2016 |
學位: | 碩士 |
摘要: | MYCN屬於MYC癌基因家族一員,且擁有轉錄因子的功能。MYCN基因片段的過度放大與神經母細胞瘤預後好壞有很大的關連性。因此了解MYCN的調控機制,對於理解神經母細胞瘤的病理機轉,與發展治療策略有很大的幫助。近年科學家找到了一種不會轉譯出蛋白質的核醣核酸──長鏈非編碼核醣核酸(long non-coding RNA,lncRNA),這種核糖核酸透過表觀遺傳、轉錄或後轉錄調控,來參與許多生物功能。由於MYCN在基因調控網路中,除了會與不同調控因子交互作用外,lncRNA也有可能藉由與MYCN的交互作用,來協助MYCN的調控。然而,MYCN和lncRNA交互作用的機制尚未清楚。在本研究中,我們提出一套計算方法,來預測可能與MYCN交互作用的lncRNA。此方法藉由神經母細胞瘤病患的基因表現資料,利用MINDy (Modulator Inference by Network Dynamics)演算法,來推論lncRNA是否扮演著調節角色(modulator),與分析此資料的存活率,尋找是否lncRNA基因表現會與MYCN基因在病人存活率上,具有協同效果(synergistic effect)。除此之外,我們也藉由lncRNA的序列資料,與MYCN蛋白序列資料,預測是否有直接的交互作用。我們共找到68個lncRNA,不但具有調節角色,也與MYCN基因表現在病人存活率上具有協同效果。從序列分析上,這些lncRNA的確有很高的機率會與MYCN蛋白有直接的交互作用。我們從lncRNA的功能分析中發現,他們會調控影響細胞死亡和細胞周期終止有關的基因,是影響或導致神經母細胞瘤形成或惡化的重要因素。本研究對於MYCN和lncRNA在神經母細胞瘤的作用機制有更進一步的了解,並期望有效的發展出適當的治療方針。 Amplification of MYCN is the most important prognostic marker in neuroblastoma, the most common extracranial solid tumor in children. Understanding the MYCN regulatory networks in neuroblastoma can gain insights into not only the mechanisms of neuroblastoma tumorigenesis, but also the development of therapeutic strategy. In recent years, a great number of long non-coding RNAs (lncRNAs) are identified due to the advances in the sequencing techniques, and these lncRNAs participate in various biological processes by functioning as epigenetic, transcriptional, and post-transcriptional regulators. Therefore, the interplay between MYCN and lncRNAs might be crucial mechanisms in neuroblastoma cells. In additional, many studies suggest that lncRNAs offer several advantages as therapeutic targets. In this study, we employed computational approaches to identify 68 candidate lncRNAs as a modulator in MYCN-regulatory networks. These lncRNAs not only interact with MYCN with a high level of confidence but also have the survival synergistic effect which may promote the risk of death. These lncRNAs might regulate genes which involve in cell death and cell cycle arrest. This work provides information about the lncRNAs in MYCN regulations, as well as insights into the mechanism of MYCN-driven tumorigenesis. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19197 |
DOI: | 10.6342/NTU201601739 |
全文授權: | 未授權 |
顯示於系所單位: | 生醫電子與資訊學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-105-1.pdf 目前未授權公開取用 | 2.94 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。