High-resolution Hi-C maps highlight multiscale 3D epigenome reprogramming during pancreatic cancer metastasis
Abstract Background Pancreatic cancer’s poor prognosis is caused by distal metastasis, which is associated with epigenetic changes. However, the role of the 3D epigenome in pancreatic cancer biology, especially its metastasis, remains unclear. Methods Here, we developed high-resolution 3D epigenomic...
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doaj-956b886cd6c1454aa1dea1300677cdef2021-08-08T11:03:35ZengBMCJournal of Hematology & Oncology1756-87222021-08-0114111910.1186/s13045-021-01131-0High-resolution Hi-C maps highlight multiscale 3D epigenome reprogramming during pancreatic cancer metastasisBo Ren0Jinshou Yang1Chengcheng Wang2Gang Yang3Huanyu Wang4Yuan Chen5Ruiyuan Xu6Xuning Fan7Lei You8Taiping Zhang9Yupei Zhao10Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeAnnoroad Gene Technology (Beijing) Co., LtdDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeAbstract Background Pancreatic cancer’s poor prognosis is caused by distal metastasis, which is associated with epigenetic changes. However, the role of the 3D epigenome in pancreatic cancer biology, especially its metastasis, remains unclear. Methods Here, we developed high-resolution 3D epigenomic maps of cells derived from normal pancreatic epithelium, primary and metastatic pancreatic cancer by in situ Hi-C, ChIP-seq, ATAC-seq, and RNA-seq to identify key genes involved in pancreatic cancer metastasis Results We found that A/B compartments, contact domains, and chromatin loops changed significantly in metastatic pancreatic cancer cells, which are associated with epigenetic state alterations. Moreover, we found that upregulated genes, which were located in switched compartments, changed contact domains, and metastasis-specific enhancer-promoter loops, were related to cancer metastasis and poor prognosis of patients with pancreatic cancer. We also found that transcription factors in specific enhancer-promoter loop formation were also associated with metastasis. Finally we demonstrated that LIPC, looped to metastasis-specific enhancers, could promote pancreatic cancer metastasis. Conclusions These results highlight the multiscale 3D epigenome reprogramming during pancreatic cancer metastasis and expand our knowledge of mechanisms of gene regulation during pancreatic cancer metastasis.https://doi.org/10.1186/s13045-021-01131-0Hi-CPancreatic cancerMetastasisEpigeneticsMulti-omics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bo Ren Jinshou Yang Chengcheng Wang Gang Yang Huanyu Wang Yuan Chen Ruiyuan Xu Xuning Fan Lei You Taiping Zhang Yupei Zhao |
spellingShingle |
Bo Ren Jinshou Yang Chengcheng Wang Gang Yang Huanyu Wang Yuan Chen Ruiyuan Xu Xuning Fan Lei You Taiping Zhang Yupei Zhao High-resolution Hi-C maps highlight multiscale 3D epigenome reprogramming during pancreatic cancer metastasis Journal of Hematology & Oncology Hi-C Pancreatic cancer Metastasis Epigenetics Multi-omics |
author_facet |
Bo Ren Jinshou Yang Chengcheng Wang Gang Yang Huanyu Wang Yuan Chen Ruiyuan Xu Xuning Fan Lei You Taiping Zhang Yupei Zhao |
author_sort |
Bo Ren |
title |
High-resolution Hi-C maps highlight multiscale 3D epigenome reprogramming during pancreatic cancer metastasis |
title_short |
High-resolution Hi-C maps highlight multiscale 3D epigenome reprogramming during pancreatic cancer metastasis |
title_full |
High-resolution Hi-C maps highlight multiscale 3D epigenome reprogramming during pancreatic cancer metastasis |
title_fullStr |
High-resolution Hi-C maps highlight multiscale 3D epigenome reprogramming during pancreatic cancer metastasis |
title_full_unstemmed |
High-resolution Hi-C maps highlight multiscale 3D epigenome reprogramming during pancreatic cancer metastasis |
title_sort |
high-resolution hi-c maps highlight multiscale 3d epigenome reprogramming during pancreatic cancer metastasis |
publisher |
BMC |
series |
Journal of Hematology & Oncology |
issn |
1756-8722 |
publishDate |
2021-08-01 |
description |
Abstract Background Pancreatic cancer’s poor prognosis is caused by distal metastasis, which is associated with epigenetic changes. However, the role of the 3D epigenome in pancreatic cancer biology, especially its metastasis, remains unclear. Methods Here, we developed high-resolution 3D epigenomic maps of cells derived from normal pancreatic epithelium, primary and metastatic pancreatic cancer by in situ Hi-C, ChIP-seq, ATAC-seq, and RNA-seq to identify key genes involved in pancreatic cancer metastasis Results We found that A/B compartments, contact domains, and chromatin loops changed significantly in metastatic pancreatic cancer cells, which are associated with epigenetic state alterations. Moreover, we found that upregulated genes, which were located in switched compartments, changed contact domains, and metastasis-specific enhancer-promoter loops, were related to cancer metastasis and poor prognosis of patients with pancreatic cancer. We also found that transcription factors in specific enhancer-promoter loop formation were also associated with metastasis. Finally we demonstrated that LIPC, looped to metastasis-specific enhancers, could promote pancreatic cancer metastasis. Conclusions These results highlight the multiscale 3D epigenome reprogramming during pancreatic cancer metastasis and expand our knowledge of mechanisms of gene regulation during pancreatic cancer metastasis. |
topic |
Hi-C Pancreatic cancer Metastasis Epigenetics Multi-omics |
url |
https://doi.org/10.1186/s13045-021-01131-0 |
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