生命科学研究2023，Vol.27Issue(6)：471-478,8.DOI:10.16605/j.cnki.1007-7847.2023.01.0112
肝癌HepG2细胞中TEAD1-增强子调控微RNA的识别与分析
Identification and Characteristic Analysis of TEAD1-Enhancers Regulating MicroRNAs in Hepatocellular Carcinoma HepG2 Cells
摘要
Abstract
The regulatory network constituted by transcription factors,enhancers,and microRNAs(miRNAs)is critical to the transcriptional regulation and progression of cancer.TEA domain transcription factor 1(TEAD1)is a member of the TEA/ATTS domain family.However,it is unclear whether TEAD1,as a cancer-related transcription factor,is involved in the enhancer-miRNA network and the occurrence and develop-ment of hepatocellular carcinoma.Herein,14 286 active enhancers that transcribe stable and unstable enhan-cer RNAs(eRNAs)were firstly identified by integrating CAGE-seq and GRO-seq data of HepG2 cell line,and confirmed to have previously reported histone modification characteristics(high H3K27ac signal and H3K4me1/H3K4me3 signal ratio).Subsequently,2 550 TEAD1-binding enhancers(EnhTEAD1)were identified by in-tegrating 35 883 TEAD1-DNA binding sites obtained from ChIP-seq data.Compared with no TEAD1-binding enhancers(EnhnoTEAD1),the expression of active enhancer markers(H3K27ac,H3K4me1 and H3K4me3)and eRNAs on EnhTEAD1 was significantly increased.Furthermore,TEAD1 may act synergistically with four transcription factors(GATA4,HNF4A,YY1,and CTCF)to promote chromatin accessibility and spatial cyclization mediated by the EnhTEAD1 region.To study the regulatory network between EnhTEAD1 and miRNAs,small RNA sequencing was performed in HepG2 cells after TEAD1 was interfered using small in-terfering RNAs(siRNAs).A total of 68 differentially expressed miRNAs(EnhTEAD1-miRNAs)regulated by EnhTEAD1 were obtained by RNA-seq and Hi-C,and were found to be significantly involved in a variety of cancer-related biological processes and pathways.In summary,the study elucidates the regulatory mecha-nism of EnhTEAD1-miRNA network in hepatocellular carcinoma,and also provides a new potential target for treatment of hepatocellular carcinoma.关键词
TEA结构域转录因子1(TEAD1)/肝细胞癌/增强子/微RNA(miRNA)Key words
TEA domain transcription factor 1(TEAD1)/hepatocellular carcinoma/enhancer/microRNA(miRNA)分类
生物科学引用本文复制引用
唐瑜泽,张茵,钟腾纬,郭志云..肝癌HepG2细胞中TEAD1-增强子调控微RNA的识别与分析[J].生命科学研究,2023,27(6):471-478,8.基金项目
四川省科技厅自然科学基金项目(2022NSFSC0779) （2022NSFSC0779）
中央高校基本科研业务费基础研究培育项目(2682023ZTPY071) （2682023ZTPY071）
传染病防治科技重大专项(2018ZX10101-003-001-008) （2018ZX10101-003-001-008）
