皮肤鳞状细胞癌相关异常甲基化基因的筛查及初步验证

发布时间：2018-04-14 00:32

本文选题：皮肤鳞状细胞癌 + RRBS　；参考：《北京协和医学院》2017年硕士论文

【摘要】：背景皮肤鳞状细胞癌是一种起源于表皮及其附属器角质形成细胞的恶性肿瘤。皮肤鳞状细胞癌发病率在皮肤恶性肿瘤中仅次于皮肤基底细胞癌,占第二位,该病的发病率较高,且处于不断上升之中。由于皮肤鳞状细胞癌的发病率日益增高,有较高的局部及远处转移率,因此对其发病机理的研究日渐引起人们的重视。表观遗传学即在不改变基因组序列的前提下,通过DNA甲基化和组蛋白修饰来调控基因表达。DNA甲基化状态的改变是引起肿瘤的一个重要因素,这种变化包括基因组整体甲基化水平降低和CpG岛局部甲基化水平的异常升高,从而导致基因组的不稳定和抑癌基因的不表达。目的筛选出候选基因,并初步验证其在皮肤鳞状细胞癌发病中的表观遗传学作用。方法采用RRBS方法检测皮肤鳞状细胞癌及癌旁组织基因组甲基化水平,采用RNA-Seq方法检测皮肤鳞状细胞癌及癌旁组织基因转录组,筛选出皮肤鳞状细胞癌异常甲基化基因,扩大样本量,采用QPCR方法进行目的基因mRNA水平的检测。结果通过RRBS和RNA-seq技术,本研究共获得了 ACACB等23个候选基因。扩大样本验证,结果显示,皮肤鳞状细胞癌中这些目的基因mRNA水平降低。结论目的基因启动子区域的异常甲基化可能参与了皮肤鳞状细胞癌的发病过程,需要进一步研究其在该病中的表观遗传功能。
[Abstract]:Background skin squamous cell carcinoma (SCC) is a malignant tumor originating from keratinocytes of epidermis and its appendages.The incidence of cutaneous squamous cell carcinoma (SCC) is second only to cutaneous basal cell carcinoma (BCC).Since the incidence of cutaneous squamous cell carcinoma (SCC) is increasing and the rate of local and distant metastasis is high, the study on the pathogenesis of SCC has attracted more and more attention.Epigenetics, which regulates gene expression and methylation through DNA methylation and histone modification without changing genomic sequence, is an important factor that causes tumor.These changes include a decrease in the global methylation level of the genome and an abnormal increase in the local methylation level of the CpG island, leading to genomic instability and non-expression of tumor suppressor genes.Objective to screen candidate genes and preliminarily verify their epigenetic role in the pathogenesis of cutaneous squamous cell carcinoma (SCC).Methods the genomic methylation level of skin squamous cell carcinoma and adjacent tissues was detected by RRBS method, and the abnormal methylation gene of skin squamous cell carcinoma was screened by RNA-Seq assay.The mRNA level of target gene was detected by QPCR method.Results A total of 23 candidate genes such as ACACB were obtained by RRBS and RNA-seq techniques.The results of expanded sample validation showed that mRNA levels of these target genes decreased in cutaneous squamous cell carcinoma.Conclusion the abnormal methylation of gene promoter region may be involved in the pathogenesis of cutaneous squamous cell carcinoma, and its epigenetic function should be further studied.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.5

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