CAJ | 학술논문

组蛋白去乙酰化酶(Histone deacetylases, HDACs)催化组蛋白去乙酰化，与细胞增殖、分化及凋亡等诸多过程密切相关。HDAC抑制剂(HADC inhibitors, HADCIs)具有潜在的抗肿瘤作用，是近年药物筛查的热点之一。近期研究提示 HDAC2可通过影响细胞代谢过程发挥抗肿瘤作用，但各类 HDACIs 调控代谢过程的机制尚待研究。本研究以肝细胞系(HepG2)为研究对象，整合比较了两种HDACIs(TSA和SAHA)的表达谱数据。在TSA处理组中，筛查到380个差异表达基因(DEGs)及35个DEGs富集的KEGG通路；SAHA处理组的表达分析印证了大多数DEGs(177/380)和富集通路(23/35)。比较分析发现，在这两类HDACIs共同影响的通路中，近一半通路(9/23)与代谢有关；近1/3共享DEGs(66/177)参与代谢过程。通过HDAC2 siRNA细胞实验证实了TSA 和 SAHA 对代谢基因的影响。本研究结果显示 HDACIs 在治疗肿瘤等代谢性疾病方面具有潜在的应用价值。
조단백거을선화매(Histone deacetylases, HDACs)최화조단백거을선화，여세포증식、분화급조망등제다과정밀절상관。HDAC억제제(HADC inhibitors, HADCIs)구유잠재적항종류작용，시근년약물사사적열점지일。근기연구제시 HDAC2가통과영향세포대사과정발휘항종류작용，단각류 HDACIs 조공대사과정적궤제상대연구。본연구이간세포계(HepG2)위연구대상，정합비교료량충HDACIs(TSA화SAHA)적표체보수거。재TSA처리조중，사사도380개차이표체기인(DEGs)급35개DEGs부집적KEGG통로；SAHA처리조적표체분석인증료대다수DEGs(177/380)화부집통로(23/35)。비교분석발현，재저량류HDACIs공동영향적통로중，근일반통로(9/23)여대사유관；근1/3공향DEGs(66/177)삼여대사과정。통과HDAC2 siRNA세포실험증실료TSA 화 SAHA 대대사기인적영향。본연구결과현시 HDACIs 재치료종류등대사성질병방면구유잠재적응용개치。
Histone deacetylases (HDACs) are responsible for catalyzing the deacetylation of histones, which closely related to many biological processes such as cell proliferation, differentiation and apoptosis. In recent years, HDAC inhibitors (HADCIs), withthe anti-tumor potential, have been hot-spots of drug screening. Although the latest studies suggested that HDAC2 might influence the metabolism, the mechanism of HDACIs in metabolic regu-lation is still unclear. Here, we integrated the gene expression profiling of HDACIs (TSA and SAHA) in hepatocellu-lar carcinoma cell (HepG2). The results showed 380 differentially expressed genes (DEGs) and 35 KEGG pathways enriched by DEGsinTSA-treatment group. Most of DEGs (177/380) and KEGG pathways (23/35) from TSA-treatment groups were confirmed by SAHA-treatment. About half of KEGG pathways (9/23) were related to metabolism ,and nearly one third of common DEGs(66/177) were involved in metabolic process. Moreover, HDAC2 siRNA experiment verified the effect of HDACIs on metabolic genes, suggesting that HDACIs potentially present a practical value to prevent tumor and other metabolism-related diseases.