Liang Yuan, Li Linlin, Xin Tian, Li Binru, Zhang Dalin
Medical Oncology Department of Thoracic Cancer (2), Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, People's Republic of China.
Department of Thyroid Surgery, The First Hospital of China Medical University, No. 155, Nanjing North Street, Shenyang 110001, Liaoning Province, People's Republic of China.
Open Med (Wars). 2021 Oct 18;16(1):1564-1582. doi: 10.1515/med-2021-0326. eCollection 2021.
This study aims to identify superenhancer (SE)-transcriptional factor (TF) regulatory network related to eight common malignant tumors based on ChIP-seq data modified by histone H3K27ac in the enhancer region of the SRA database.
H3K27ac ChIP-seq data of eight common malignant tumor samples were downloaded from the SRA database and subjected to comparison with the human reference genome hg19. TFs regulated by SEs were screened with HOMER software. Core regulatory circuitry (CRC) in malignant tumor samples was defined through CRCmapper software and validated by RNA-seq data in TCGA. The findings were substantiated in bladder cancer cell experiments.
Different malignant tumors could be distinguished through the H3K27ac signal. After SE identification in eight common malignant tumor samples, 35 SE-regulated genes were defined as malignant tumor-specific. SE-regulated specific TFs effectively distinguished the types of malignant tumors. Finally, we obtained 60 CRC TFs, and SMAD3 exhibited a strong H3K27ac signal in eight common malignant tumor samples. experimental data verified the presence of a SE-TF regulatory network in bladder cancer, and SE-TF regulatory network enhanced the malignant phenotype of bladder cancer cells.
The SE-TF regulatory network with SMAD3 as the core TF may participate in the carcinogenesis of malignant tumors.
本研究旨在基于SRA数据库增强子区域中经组蛋白H3K27ac修饰的ChIP-seq数据，识别与八种常见恶性肿瘤相关的超级增强子（SE）-转录因子（TF）调控网络。
从SRA数据库下载八种常见恶性肿瘤样本的H3K27ac ChIP-seq数据，并与人类参考基因组hg19进行比对。使用HOMER软件筛选由SE调控的TF。通过CRCmapper软件定义恶性肿瘤样本中的核心调控回路（CRC），并通过TCGA中的RNA-seq数据进行验证。研究结果在膀胱癌细胞实验中得到证实。
通过H3K27ac信号可区分不同的恶性肿瘤。在八种常见恶性肿瘤样本中鉴定出SE后，35个受SE调控的基因被定义为恶性肿瘤特异性基因。受SE调控的特异性TF能有效区分恶性肿瘤类型。最后，我们获得了60个CRC TF，其中SMAD3在八种常见恶性肿瘤样本中表现出强烈的H3K27ac信号。实验数据证实了膀胱癌中存在SE-TF调控网络，且SE-TF调控网络增强了膀胱癌细胞的恶性表型。
以SMAD3为核心TF的SE-TF调控网络可能参与恶性肿瘤的发生发展。
