2011-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/701626摘要：這些“非遺傳＂機制，包括DNA甲基化，組蛋白後修飾，核小體重塑及微型RNA。破壞這些相互作用的系統可能會導致基因的異常表達或靜默，導致'非遺傳疾病'。組蛋白甲基轉移酶在促進人類癌症的惡化已被報導。然而，組蛋白甲基轉移酶G9a，在癌症轉移的角色仍不清。我們最近的研究證實，作為甲基轉移酶G9a是肺癌轉移的調節者。為探討甲基轉移酶G9a在癌症生物學中，我們已經在卵巢癌模型研究轉移酶G9a的功能。我們的初步結果強烈支持，轉移酶G9a與卵巢癌腹膜傳播。到目前為止，治療與 DNA去甲基化劑和HDAC抑製劑是基於傳統的蛋白編碼腫瘤抑制基因，通過微型miRNA組蛋白- DNA的去甲基化的治療建議新的治療策略的可能性。因此，我們建議這個項目推出的關鍵作用轉移酶G9a和後生的miRNA在卵巢癌。雖然非遺傳調控和微型RNA都發揮了重要作用，卵巢癌，這兩者之間的途徑是知之甚少。了解組蛋白修飾酶之間的交互作用 -轉移酶G9a和調控轉移酶G9a的微型RNA，將有助於開發新的治療策略的搶救治療的非遺傳機制的微型RNA。我們的具體目標如下：1。要定義中的作用在卵巢癌發生轉移酶G9a和癌症的進展。2。要識別 miRNA的調控轉移酶G9a調解的生物學功能。3。探討表觀遺傳和分子機制的miRNA介導的轉移酶G9a監管。4。為了研究的臨床意義及其下游轉移酶G9a miRNA與癌症患者。<br> Abstract: These “epigenetic” mechanisms include DNA methylation, post-translational histonemodifications, nucleosome remodeling and non-coding RNAs. Disruption of one or other ofthese interacting systems can lead to inappropriate expression or silencing of genes, resultingin ‘epigenetic diseases’. The role of HMTs in promoting tumorigenesis and the progression ofhuman cancers has begun to emerge. However, the functional roles of members of the HMTfamily such as G9a in cancer remain obscure. We have recently verified that G9a function asa regulator of metastasis in lung cancer. To elaborate the role of G9a in cancer biology, wehave investigated the functional role of G9a in ovarian cancer model. Our preliminary datastrongly support that G9a is linked to peritoneal dissemination in ovarian cancer. Until now,therapy with DNA demethylating agents and HDAC inhibitors has been based on classicprotein-coding tumor-suppressor genes, but the possibility of rescuing the epigeneticregulatory effects of miRNAs by means of histone-DNA-demethylation treatment suggestsnew epigenetic treatment strategies that are worthy of further exploration. We thereforeproposed this project to unveil the critical role of G9a and epigenetic regulatory miRNA inovarian carcinogenesis. Though both epigenetic regulation and miRNA play an importantfunction in ovarian carcinogenesis, the crosstalk between these two pathways are largelyunknown. Understanding the crosstalk between histone modification enzyme - G9a andG9a regulatory miRNAs would be helpful to develop new treatment strategies of epigenetictherapy by rescuing epigenetic regulatory miRNAs. Our specific aim as followed:1. To define the roles of G9a in ovarian cancer carcinogenesis and cancer progression.2. To identify miRNAs regulating G9a mediating biological functions.3. To investigate the epigenetic and molecular mechanism of miRNA-mediated G9aregulation.4. To study the clinical significance of miRNA and its downstream G9a in cancer patients.組蛋白轉移酶G9a微型核糖核酸後遺傳卵巢癌histone methyl transferase G9amiRNAepigeneticovarian cancer