2011-01-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/657016摘要：癌轉移是癌症治療的障礙之一，也常是臨床治療失敗的主因。外基因(epigenetic)調控中的DNA甲基化被認為在腫瘤發生和轉移中扮演重要角色。基因啟動子上CG長序列區域的甲基化程度改變會促使基因表達異常，因此探討DNA甲基化與肺癌發生和轉移之關係，將有利於癌症致病機轉了解，診斷及治療。因此，我們提出DNA甲基化可以調控癌症轉移的假說。本計畫將: (i) 利用DNA甲基化晶片分析不同程度轉移能力的肺癌細胞株，篩選出具受外基因調控之促癌和抑癌移轉基因；(ii) 以肺癌細胞及實驗動物模式探討促癌和抑癌移轉之相關基因生物功能；(iii) 利用篩選出基因的啟動子甲基化的型態來設計出高效能的甲基化檢測晶片，運用於臨床上預測病人的預後狀態；(iv) 研究上述篩選出基因受外基因調控之機制，以釐清外基因調控和癌症轉移的關係。此外，將利用甲基化晶片平台來篩選出高度專一性的DNA甲基化抑制劑，以助減緩或抑制癌症移轉。希望藉由本研究釐清癌轉移與外基因調控之關係，並發展高效能及高專一性之診斷方法及藥物。<br> Abstract: Metastasis is a common feature in advanced cancers. For treatment, the highly invasive and metastatic characteristics of lung cancer are common cause of treatment failure. Recent studies highlight the important role of epigenomics in the progression of cancer. As an alternative mechanism, hypermethylation of CpG islands spanning the promoter regions of tumor suppressor genes is a common and important mechanism in carcinogenesis. We hypothesize that cancer metastasis can be epigenetically controlled by DNA methylation. Specifically, we will: (i) use DMH methylation array to screen the highly potential metastasis-suppressor genes that are regulated by DNA methylation during cancer metastasis; (ii) further confirm these highly potential metastasis-suppressor genes in vitro and in vivo models; (iii) use these methylation patterns of candidate genes on promoter region to develop high efficiency methylation chip which can use to predict clinical outcome; (iv) based on this chip, we will investigate the molecular mechanism of epigenetic modulation of invasion suppressors; clarify the epigenetic control of cancer metastasis and explore the possibility of identification of specific demethylation agents that can suppress cancer metastasis. The results obtained from this study are anticipated to lead to the finding of optimal compound which can later be advanced to anticancer clinical trialsDNA甲基化mir-135bTROP2