Oncogenic enhancers drive esophageal squamous cell carcinogenesis and metastasis.
Oncogenic enhancers drive esophageal squamous cell carcinogenesis and metastasis.
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致癌增强剂驱动食管鳞状细胞癌变和转移
DOI：
10.1038/s41467-021-24813-2
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发表时间：
2021-07-22
影响因子：
16.6
通讯作者：
Qiao Y
中科院分区：
文献类型：
--
作者：
Ye B;Fan D;Xiong W;Li M;Yuan J;Jiang Q;Zhao Y;Lin J;Liu J;Lv Y;Wang X;Li Z;Su J;Qiao Y
顺式元件及其畸变在食管鳞状细胞癌（ESCC，进一步缩写为 EC）中的作用仍不清楚。在这里，我们调查了原发性 EC、转移性淋巴结癌 (LNC) 和邻近正常 (Nor) 食管组织中的 28 个 H3K27ac 标记的活性增强子谱和 50 个转录组。相对于 Nor，在 EC 和 LNC 样本中分别鉴定出数千个获得或丢失的增强子以及数百个改变的推定超级增强子，其中有大量常见的获得或丢失的增强子。此外，这些差异增强子导致 EC 和 LNC 中的转录组畸变。我们还揭示了假定的驱动肿瘤转录因子，其消耗会减少细胞增殖和迁移。使用化学抑制剂来抑制获得的超级增强的预测目标表明 HSP90AA1 和 PDE4B 是 ESCC 的潜在治疗目标。因此，我们的表观基因组分析揭示了 ESCC 致癌和转移过程中重编程调控元件的概要，以揭示癌症治疗的有希望的靶点。
The role ofcis-elements and their aberrations remains unclear in esophageal squamous cell carcinoma (ESCC, further abbreviated EC). Here we survey 28 H3K27ac-marked active enhancer profiles and 50 transcriptomes in primary EC, metastatic lymph node cancer (LNC), and adjacent normal (Nor) esophageal tissues. Thousands of gained or lost enhancers and hundreds of altered putative super-enhancers are identified in EC and LNC samples respectively relative to Nor, with a large number of common gained or lost enhancers. Moreover, these differential enhancers contribute to the transcriptomic aberrations in ECs and LNCs. We also reveal putative driver onco-transcription factors, depletion of which diminishes cell proliferation and migration. The administration of chemical inhibitors to suppress the predicted targets of gained super-enhances reveals HSP90AA1 and PDE4B as potential therapeutic targets for ESCC. Thus, our epigenomic profiling reveals a compendium of reprogrammedcis-regulatory elements during ESCC carcinogenesis and metastasis for uncovering promising targets for cancer treatment.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
30.8
作者：
Levine, David M.;Ek, Weronica E.;Zhang, Rui;Liu, Xinxue;Onstad, Lynn;Sather, Cassandra;Lao-Sirieix, Pierre;Gammon, Marilie D.;Corley, Douglas A.;Shaheen, Nicholas J.;Bird, Nigel C.;Hardie, Laura J.;Murray, Liam J.;Reid, Brian J.;Chow, Wong-Ho;Risch, Harvey A.;Nyren, Olof;Ye, Weimin;Liu, Geoffrey;Romero, Yvonne;Bernstein, Leslie;Wu, Anna H.;Casson, Alan G.;Chanock, Stephen J.;Harrington, Patricia;Caldas, Isabel;Debiram-Beecham, Irene;Caldas, Carlos;Hayward, Nicholas K.;Pharoah, Paul D.;Fitzgerald, Rebecca C.;MacGregor, Stuart;Whiteman, David C.;Vaughan, Thomas L.
通讯作者：
Vaughan, Thomas L.
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
30.8
作者：
Dulak, Austin M.;Stojanov, Petar;Peng, Shouyong;Lawrence, Michael S.;Fox, Cameron;Stewart, Chip;Bandla, Santhoshi;Imamura, Yu;Schumacher, Steven E.;Shefler, Erica;McKenna, Aaron;Carter, Scott L.;Cibulskis, Kristian;Sivachenko, Andrey;Saksena, Gordon;Voet, Douglas;Ramos, Alex H.;Auclair, Daniel;Thompson, Kristin;Sougnez, Carrie;Onofrio, Robert C.;Guiducci, Candace;Beroukhim, Rameen;Zhou, Zhongren;Lin, Lin;Lin, Jules;Reddy, Rishindra;Chang, Andrew;Landrenau, Rodney;Pennathur, Arjun;Ogino, Shuji;Luketich, James D.;Golub, Todd R.;Gabriel, Stacey B.;Lander, Eric S.;Beer, David G.;Godfrey, Tony E.;Getz, Gad;Bass, Adam J.
通讯作者：
Bass, Adam J.