Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor SGI-110 in Hepatocellular Carcinoma Cells [gene expression]. Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor SGI-110 in Hepatocellular Carcinoma Cells [gene expression]

There is an urgent need for developing more effective therapies for aggressive hepatocellular carcinoma (HCC). Guadecitabine (SGI-110) is a second-generation DNA methyltransferase inhibitor (DNMTi) currently in clinical trials for HCC and shows greater stability and performance over first generation DNMTis. The aim of this study is to identify potential therapeutic targets of SGI-110 for clinical trials. Overall design: HCC cell lines (SNU398, HepG2 and SNU475) were used to evaluate effects of SGI-110 by an integrative analysis of DNA methylation, nucleosome accessibility and gene expression profiles following the transient SGI-110 treatment and its clinical relevance by comparing to HCC clinical data from TCGA.

针对侵袭性肝细胞癌（hepatocellular carcinoma，HCC），目前亟需开发更为有效的治疗策略。呱德西他滨（Guadecitabine，SGI-110）是第二代DNA甲基转移酶抑制剂（DNA methyltransferase inhibitor，DNMTi），目前正针对HCC开展临床试验，相较于第一代DNMTi类药物展现出更优的稳定性与药效。本研究旨在筛选可用于SGI-110临床试验的潜在治疗靶点。整体实验设计：本研究采用HCC细胞系（SNU398、HepG2及SNU475），对SGI-110进行瞬时处理后，通过整合分析样本的DNA甲基化、核小体可及性与基因表达谱，并对比癌症基因组图谱（The Cancer Genome Atlas，TCGA）中的HCC临床数据以验证其临床相关性，以此评估SGI-110的生物学效应。