3D genome landscape of primary and metastatic colorectal carcinoma reveals the regulatory mechanism of tumorigenic and metastatic gene expression
Abstract Colorectal carcinoma (CRC) is a deadly cancer with an aggressive nature, and how CRC tumor cells manage to translocate and proliferate in a new tissue environment remains not fully understood. Recently, higher-order chromatin structures and spatial genome organization are increasingly impli...
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| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07647-2 |
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| author | Xiang Xu Jingbo Gan Zhaoya Gao Ruifeng Li Dandan Huang Lin Lin Yawen Luo Qian Yang Jingxuan Xu Yaru Li Qing Fang Ting Peng Yaqi Wang Zihan Xu An Huang Haopeng Hong Fuming Lei Wensheng Huang Jianjun Leng Tingting Li Xiaochen Bo Hebing Chen Cheng Li Jin Gu |
| author_facet | Xiang Xu Jingbo Gan Zhaoya Gao Ruifeng Li Dandan Huang Lin Lin Yawen Luo Qian Yang Jingxuan Xu Yaru Li Qing Fang Ting Peng Yaqi Wang Zihan Xu An Huang Haopeng Hong Fuming Lei Wensheng Huang Jianjun Leng Tingting Li Xiaochen Bo Hebing Chen Cheng Li Jin Gu |
| author_sort | Xiang Xu |
| collection | DOAJ |
| description | Abstract Colorectal carcinoma (CRC) is a deadly cancer with an aggressive nature, and how CRC tumor cells manage to translocate and proliferate in a new tissue environment remains not fully understood. Recently, higher-order chromatin structures and spatial genome organization are increasingly implicated in diseases including cancer, but in-depth studies of three-dimensional genome (3D genome) of metastatic cancer are currently lacking, preventing the understanding of the roles of genome organization during metastasis. Here we perform multi-omics profiling of matched normal colon, primary tumor, lymph node metastasis, liver metastasis and normal liver tissue from CRC patients using Hi-C, ATAC-seq and RNA-seq technologies. We find that widespread alteration of 3D chromatin structure is accompanied by dysregulation of genes including SPP1 during the tumorigenesis or metastasis of CRC. Remarkably, the hierarchy of topological associating domain (TAD) changes dynamically, which challenges the traditional view that the TAD structure between tumor and normal tissue is conservative. In addition, we define compartment stability score to measure large-scale alteration in metastatic tumors. To integrate multi-omics data and recognize candidate genes driving cancer metastasis, a pipeline is developed based on Hi-C, RNA-seq and ATAC-seq data. And three candidate genes ARL4C, FLNA, and RGCC are validated to be associated with CRC cell migration and invasion using in vitro knockout experiments. Overall, these data resources and results offer new insights into the involvement of 3D genome in cancer metastasis. |
| format | Article |
| id | doaj-art-6e5ac187af4c4f91bec2003dcf58dc12 |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-6e5ac187af4c4f91bec2003dcf58dc122025-08-20T01:54:25ZengNature PortfolioCommunications Biology2399-36422025-03-018111610.1038/s42003-025-07647-23D genome landscape of primary and metastatic colorectal carcinoma reveals the regulatory mechanism of tumorigenic and metastatic gene expressionXiang Xu0Jingbo Gan1Zhaoya Gao2Ruifeng Li3Dandan Huang4Lin Lin5Yawen Luo6Qian Yang7Jingxuan Xu8Yaru Li9Qing Fang10Ting Peng11Yaqi Wang12Zihan Xu13An Huang14Haopeng Hong15Fuming Lei16Wensheng Huang17Jianjun Leng18Tingting Li19Xiaochen Bo20Hebing Chen21Cheng Li22Jin Gu23Department of Gastrointestinal Surgery, Peking University Shougang HospitalCenter for Bioinformatics, School of Life Sciences, Center for Statistical Science, Peking UniversityDepartment of Gastrointestinal Surgery, Peking University Shougang HospitalCenter for Bioinformatics, School of Life Sciences, Center for Statistical Science, Peking UniversityCenter for Precision Diagnosis and Treatment of Colorectal Carcinoma and Inflammatory Diseases, Peking University Health Science CenterAcademy of Military Medical SciencesAcademy of Military Medical SciencesAcademy of Military Medical SciencesDepartment of Gastrointestinal Surgery, Peking University Shougang HospitalAcademy of Military Medical SciencesCenter for Bioinformatics, School of Life Sciences, Center for Statistical Science, Peking UniversityCenter for Bioinformatics, School of Life Sciences, Center for Statistical Science, Peking UniversityCenter for Bioinformatics, School of Life Sciences, Center for Statistical Science, Peking UniversityCenter for Bioinformatics, School of Life Sciences, Center for Statistical Science, Peking UniversityKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & InstituteDepartment of Gastrointestinal Surgery, Peking University Shougang HospitalDepartment of Gastrointestinal Surgery, Peking University Shougang HospitalCenter for Precision Diagnosis and Treatment of Colorectal Carcinoma and Inflammatory Diseases, Peking University Health Science CenterCenter for Bioinformatics, School of Life Sciences, Center for Statistical Science, Peking UniversityAcademy of Military Medical SciencesAcademy of Military Medical SciencesCenter for Bioinformatics, School of Life Sciences, Center for Statistical Science, Peking UniversityDepartment of Gastrointestinal Surgery, Peking University Shougang HospitalAbstract Colorectal carcinoma (CRC) is a deadly cancer with an aggressive nature, and how CRC tumor cells manage to translocate and proliferate in a new tissue environment remains not fully understood. Recently, higher-order chromatin structures and spatial genome organization are increasingly implicated in diseases including cancer, but in-depth studies of three-dimensional genome (3D genome) of metastatic cancer are currently lacking, preventing the understanding of the roles of genome organization during metastasis. Here we perform multi-omics profiling of matched normal colon, primary tumor, lymph node metastasis, liver metastasis and normal liver tissue from CRC patients using Hi-C, ATAC-seq and RNA-seq technologies. We find that widespread alteration of 3D chromatin structure is accompanied by dysregulation of genes including SPP1 during the tumorigenesis or metastasis of CRC. Remarkably, the hierarchy of topological associating domain (TAD) changes dynamically, which challenges the traditional view that the TAD structure between tumor and normal tissue is conservative. In addition, we define compartment stability score to measure large-scale alteration in metastatic tumors. To integrate multi-omics data and recognize candidate genes driving cancer metastasis, a pipeline is developed based on Hi-C, RNA-seq and ATAC-seq data. And three candidate genes ARL4C, FLNA, and RGCC are validated to be associated with CRC cell migration and invasion using in vitro knockout experiments. Overall, these data resources and results offer new insights into the involvement of 3D genome in cancer metastasis.https://doi.org/10.1038/s42003-025-07647-2 |
| spellingShingle | Xiang Xu Jingbo Gan Zhaoya Gao Ruifeng Li Dandan Huang Lin Lin Yawen Luo Qian Yang Jingxuan Xu Yaru Li Qing Fang Ting Peng Yaqi Wang Zihan Xu An Huang Haopeng Hong Fuming Lei Wensheng Huang Jianjun Leng Tingting Li Xiaochen Bo Hebing Chen Cheng Li Jin Gu 3D genome landscape of primary and metastatic colorectal carcinoma reveals the regulatory mechanism of tumorigenic and metastatic gene expression Communications Biology |
| title | 3D genome landscape of primary and metastatic colorectal carcinoma reveals the regulatory mechanism of tumorigenic and metastatic gene expression |
| title_full | 3D genome landscape of primary and metastatic colorectal carcinoma reveals the regulatory mechanism of tumorigenic and metastatic gene expression |
| title_fullStr | 3D genome landscape of primary and metastatic colorectal carcinoma reveals the regulatory mechanism of tumorigenic and metastatic gene expression |
| title_full_unstemmed | 3D genome landscape of primary and metastatic colorectal carcinoma reveals the regulatory mechanism of tumorigenic and metastatic gene expression |
| title_short | 3D genome landscape of primary and metastatic colorectal carcinoma reveals the regulatory mechanism of tumorigenic and metastatic gene expression |
| title_sort | 3d genome landscape of primary and metastatic colorectal carcinoma reveals the regulatory mechanism of tumorigenic and metastatic gene expression |
| url | https://doi.org/10.1038/s42003-025-07647-2 |
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