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標題: | 探討微小核醣核酸−ETV1−KIT之路徑在胃腸道基質瘤中對於腫瘤生成之影響 Investigation of the miR-ETV1-KIT Axis in the development of Gastrointestinal Stromal Tumors |
作者: | Po-Chen Kuo 郭柏辰 |
指導教授: | 李財坤(Tsai-Kun Li) |
關鍵字: | 胃腸道基質瘤,KIT受體酪氨酸激?,ETV1轉錄因子,微小核醣核酸,腫瘤生成,非錨定依賴性生長, Gastrointestinal stromal tumor,GIST,KIT receptor tyrosine kinase,ETV1 transcription factor,microRNA,anchorage-independent growth,tumorigenesis, |
出版年 : | 2016 |
學位: | 碩士 |
摘要: | 胃腸道基質瘤(Gastrointestinal stromal tumors,簡稱作GISTs)是在腸胃道中,最常發生的原發性間葉(mesenchyme)瘤;此腫瘤以高度表現KIT受體酪氨酸激酶為特點;大多數(約85%)胃腸道基質瘤帶有KIT基因突變而使KIT持續活化而導致腫瘤的發生;此外,胃腸道基質瘤也會高度表現ETV1轉錄因子;過去認為KIT會與ETV1協同作用而導致胃腸道基質瘤的腫瘤生成。本論文首先藉由在不同的胃腸道基質瘤細胞株進行轉染來探討KIT與ETV1的交互作用與調控機制;並使用非錨定依賴性生長實驗來探討KIT與ETV1對胃腸道基質瘤腫瘤生成的影響。實驗結果顯示,ETV1除了可以對KIT進行正向調控之外,還可以增加胃腸道基質瘤的腫瘤生成能力;然而在具有Imatinib抗藥性的胃腸道基質瘤的細胞中,KIT或許不是ETV1的最主要上游調控因子。本論文的另一目標在於探討微小核醣核酸(miR-193a-3p、miR-296-5p、miR-330-5p、miR-627和miR-1237)是否會對ETV1進行調控進而影響胃腸道基質瘤的腫瘤生成;其實驗方法為在GIST48b細胞株中將上述微小核醣核酸中大量表現後進行非錨定依賴性生長實驗;目前實驗結果顯示,這些微小核醣核酸具有調控ETV1-KIT路徑的作用和影響胃腸道基質瘤的腫瘤生成能力;其中,miR-193a-3p對於胃腸道基質瘤的腫瘤生成最具抑癌潛力。綜上所述,此微小核醣核酸-ETV1-KIT路徑在胃腸道基質瘤的腫瘤生成的調控機制可在未來持續研究探討。 Gastrointestinal stromal tumors (GISTs) were the most common primary mesenchymal tumor affecting the gastrointestinal tract. GISTs were characterized by the expression of KIT receptor tyrosine kinase. The majority (~ 85%) of GISTs carried active mutations of KIT gene, which were crucial for GISTs development. In addition, the ETV1 transcription factor was also highly expressed in GISTs. Previously, KIT was thought to cooperate with ETV1 in GIST tumorigenesis. In this thesis, the functional and genetic interactions between KIT and ETV1 were studied by a serious of transfection experiments in different GIST cell lines. The tumorigenesis roles of KIT and ETV1 were also investigated by the anchorage-independent growth assays. The results revealed that ETV1 could positively regulate KIT expression and enhance tumorigenicity in GISTs. Nevertheless, KIT played less role in regulating ETV1 in the Imatinib-resistant GIST cell lines. Another aim of this thesis was to investigate the roles of the microRNAs (miR-193a-3p, miR-296-5p, miR-330-5p, miR-627 and miR-1237) in regulating GIST tumorigenesis by targeting ETV1. The anchorage-independent growth assays were performed after the ectopic expression of these microRNAs in GIST48b cell line. Current results revealed that these microRNAs involved in regulation of the ETV1-KIT axis and GIST tumorigenesis with the miR-193a-3p showed the greatest potential to serve as a tumor suppressor to govern GIST initiation. Together, the regulatory mechanisms of the miR-ETV1-KIT axis in GIST tumorigenesis shall be further investigated. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/3856 |
DOI: | 10.6342/NTU201601168 |
全文授權: | 同意授權(全球公開) |
顯示於系所單位: | 微生物學科所 |
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