项目名称: DNA甲基化修饰在子宫平滑肌肉瘤发病机制中的作用研究
项目编号: No.81502251
项目类型: 青年科学基金项目
立项/批准年度: 2016
项目学科: 医药、卫生
项目作者: 张青
作者单位: 山东大学
项目金额: 18万元
中文摘要: 子宫平滑肌肉瘤(ULMS)恶性程度高,预后差,其发病机制尚不清楚。DNA甲基化是恶性肿瘤的重要调控机制,本研究中课题组首先利用全基因组DNA甲基化芯片和mRNA表达谱芯片技术,从宏观上阐述DNA甲基化在ULMS进展中的作用,同时筛选出数个子宫平滑肌肉瘤特异性甲基化基因(LMS-SMGs),在组织标本、体内及体外实验中进一步筛选明确LMS-SMGs的生物学功能;课题组在前期工作中已经从多角度证实了不典型性子宫平滑肌瘤(ALM)和ULMS有相似的分子生物学改变,进而提出了“ALM可能是ULMS癌前病变”这一假说,本课题通过在比较ALM和ULMS之间LMS-SMGs的DNA甲基化和蛋白表达状态,从表观遗传学角度为“ALM可能是ULMS癌前病变”这一假说提供证据;本研究将为明确ULMS的甲基化调控和分子起源提供证据,对ULMS的早期诊断、新药靶点研发及改善预后等具有重要的临床意义。
中文关键词: 子宫平滑肌肉瘤;不典型性子宫平滑肌瘤;DNA甲基化;mRNA表达谱;癌前病变
英文摘要: Uterine leiomyosarcoma (ULMS) is a gynecological malignancy with poor prognosis, but the mechanism of ULMS tumorigenesis is largely unknown. DNA methylation plays a great role in malignant tumor pathogenesis and progression. In this study, whole genomic DNA methylation microarray is conducted together with mRNA expression profiling to explore the possible participation of DNA methylation in ULMS. By combination of the two microarray data, we intend to screen several potential uterine leiomyosarcoma specific methylation genes (LMS-SMGs). Then tissue samples, in vitro and in vivo assays will be used to confirm these genes and their biological functions. Our preliminary data suggested that atypical leiomyoma (ALM) would be precancerous lesion of ULMS as they shared significantly similar molecular pattern. This study will provide further evidence to support the hypothesis that ALM is precancerous lesion of ULMS by comparing the expression of LMS-SMGs in ALM and ULMS. Overall, this project will provide new perspectives for the origin of ULMS and regulation of ULMS by DNA methylation and furthermore promote the progress of early diagnosis, new therapeutics and prognosis for ULMS.
英文关键词: leiomyosarcoma;atypical leiomyoma;DNA methylation;mRNA profiling;precancerous leision