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博碩士論文 etd-0706112-173625 詳細資訊
Title page for etd-0706112-173625
論文名稱
Title
STAT3增加微小核酸miR-92a表現對肺癌細胞RECK基因的調控
STAT3-upregulated miR-92a in the control RECK expression in lung cancer cells
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
70
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2012-06-13
繳交日期
Date of Submission
2012-07-06
關鍵字
Keywords
微小RNA、肺癌
RECK, miR-92a, STAT3
統計
Statistics
本論文已被瀏覽 5708 次,被下載 1026
The thesis/dissertation has been browsed 5708 times, has been downloaded 1026 times.
中文摘要
肺癌是目前癌症造成死亡的常見疾病。STAT3 (signal transducer and activator of transcription 3)是一種細胞內的轉錄因子,並且已被報導可促進腫瘤的生成,當細胞內STAT3過度表現時對肺癌的發生有極大的相關性。RECK (reversion- inducing cysteine-rich protein with Kazal motifs)目前已知為一鑲嵌在細胞膜上的醣蛋白,可抑制MMP (matrix metalloproteinase)分解細胞外基質,以及抑制血管新生,進而減少腫瘤的侵襲及轉移,因此RECK亦為腫瘤抑制基因;在我們實驗室先前的研究已證明如何調控RECK基因轉錄的發生。但近年來有許多報導指出微小RNA (microRNA、miR)在調控基因表現及癌症的發生過程中亦扮演重要的角色,其中具致癌性的miR-17-92a cluster在肺癌組織中呈現過度表現。在本篇論文中我們探討在肺癌細胞中,當STAT3過度表現時是否會藉由microRNA來調控RECK基因的轉錄後表現。我們的實驗中發現miR- 17-92a cluster其中的一個成員,miR-92a可以結合到RECK 3’UTR (untranslated region),並且當抑制STAT3過度表現的現象後亦可抑制miR-92a的表現;此外,將細胞大量表現miR-92a後會造成RECK的蛋白質表現量下降,而在STAT3高度表現的細胞株中,抑制miR-92a的過度表現後可回復RECK的蛋白質表現量,並減少細胞的侵襲及轉移能力。綜合以上的實驗結果,我們可推論在肺癌細胞中STAT3可藉由增加miR-92a表現來調控RECK基因的表現。
Abstract
Lung cancer is the common cause of cancer death. STAT3 (signal transducer and activator of transcription 3) has been reported to be an oncogenic transcription factor and high expression of STAT3 is associated with lung cancer progression. RECK (reversion-inducing cysteine-rich protein with Kazal motifs) is a tumor suppressor gene and a membrane-anchored glycoprotein that reduces the matrix metalloproteinases (MMPs)-induced destruction of extra-cellular matrix (ECM) and tumor metastasis. RECK also inhibits tumor angiogenesis. We have previously elucidated the transcriptional regulation of RECK gene. Recently, microRNAs (miRs) are shown to be key players in gene regulation and cancer progression. In this study, we try to elucidate whether ovexpression of STAT3 can affect microRNA expression to regulate RECK via post-transcriptional modulation. miR-17-92a cluster is a well-known oncomir which is highly expressed in lung cancer tissue. We find that miR-92a, a member of miR-17-92a cluster can target RECK 3’UTR. In addition, our data suggest that STAT3 regulates the expression of miR-92a and inhibition of STAT3 can decrease miR-92a expression. Furthermore, overexpression of miR-92a can decrease RECK protein level. While knockdown of miR-92a expression in STAT3-overexpressing cell lines can restore RECK protein level, and reduce invasion and migration. Results of this study suggest that STAT3 up-regulates miR-92a to inhibit RECK expression and promote lung cancer metastasis.
目次 Table of Contents
Abstract in Chinese 3
Abstract in English 4
Contents 5
Abbreviations 6
1. Introduction 7
2. Materials and Methods 13
3. Results and Figures 33
4. Discussion 55
5. Reference 59
6. Appendix 65
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