Activation of TC10-Like Transcription by Lysine Demethylase KDM4B in Colorectal Cancer Cells
Malignant colorectal cancers (CRCs) are characterized by enhanced migration and invasion thus acquiring the ability to metastasize. We have previously shown that the small GTPase TC10-like (TCL) contributes to aggressive migration and invasion in malignant CRC cells. TCL expression is differentially...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.617549/full |
| _version_ | 1819021895643693056 |
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| author | Baoyu Chen Yuwen Zhu Junliang Chen Yifei Feng Yifei Feng Yong Xu Yong Xu |
| author_facet | Baoyu Chen Yuwen Zhu Junliang Chen Yifei Feng Yifei Feng Yong Xu Yong Xu |
| author_sort | Baoyu Chen |
| collection | DOAJ |
| description | Malignant colorectal cancers (CRCs) are characterized by enhanced migration and invasion thus acquiring the ability to metastasize. We have previously shown that the small GTPase TC10-like (TCL) contributes to aggressive migration and invasion in malignant CRC cells. TCL expression is differentially expressed in CRC cells and can be upregulated by hypoxia although the underlying epigenetic mechanism is not fully appreciated. Here, we report that differential TCL expression in CRC cells appeared to be associated with histone H3K9 methylation. RNAi screening revealed that the lysine demethylase KDM4B was essential for TCL transcription in CRC cells. KDM4B interacted with and was recruited by the sequence-specific transcription factor ETS-related gene 1 (ERG1) to the TCL promoter to activate transcription. Mechanistically, KDM4B mediated H3K9 demethylase facilitated the assembly of pre-initiation complex (PIC) on the TCL promoter. KDM4B knockdown attenuated migration and invasion of CRC cells. Importantly, KDM4B expression was upregulated in human CRC specimens of advanced stages compared to those of lower grades and associated with poor prognosis. Together, these data uncover a novel epigenetic mechanism underlying malignant transformation of CRC cells and suggest that KDM4B may be considered as a therapeutic target in CRC intervention. |
| first_indexed | 2024-12-21T04:14:22Z |
| format | Article |
| id | doaj.art-50a3bd8528ed440aa9309aa3d7984a49 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T04:14:22Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-50a3bd8528ed440aa9309aa3d7984a492022-12-21T19:16:21ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-06-01910.3389/fcell.2021.617549617549Activation of TC10-Like Transcription by Lysine Demethylase KDM4B in Colorectal Cancer CellsBaoyu Chen0Yuwen Zhu1Junliang Chen2Yifei Feng3Yifei Feng4Yong Xu5Yong Xu6Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, ChinaKey Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, ChinaDepartment of Pathophysiology, Wuxi Medical School, Jiangnan University, Wuxi, ChinaDepartment of Colorectal Surgery, The First Hospital Affiliated With Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First School of Clinical Medicine, Nanjing Medical University, Nanjing, ChinaKey Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, ChinaInstitute of Biomedical Research, Liaocheng University, Liaocheng, ChinaMalignant colorectal cancers (CRCs) are characterized by enhanced migration and invasion thus acquiring the ability to metastasize. We have previously shown that the small GTPase TC10-like (TCL) contributes to aggressive migration and invasion in malignant CRC cells. TCL expression is differentially expressed in CRC cells and can be upregulated by hypoxia although the underlying epigenetic mechanism is not fully appreciated. Here, we report that differential TCL expression in CRC cells appeared to be associated with histone H3K9 methylation. RNAi screening revealed that the lysine demethylase KDM4B was essential for TCL transcription in CRC cells. KDM4B interacted with and was recruited by the sequence-specific transcription factor ETS-related gene 1 (ERG1) to the TCL promoter to activate transcription. Mechanistically, KDM4B mediated H3K9 demethylase facilitated the assembly of pre-initiation complex (PIC) on the TCL promoter. KDM4B knockdown attenuated migration and invasion of CRC cells. Importantly, KDM4B expression was upregulated in human CRC specimens of advanced stages compared to those of lower grades and associated with poor prognosis. Together, these data uncover a novel epigenetic mechanism underlying malignant transformation of CRC cells and suggest that KDM4B may be considered as a therapeutic target in CRC intervention.https://www.frontiersin.org/articles/10.3389/fcell.2021.617549/fulltranscriptional regulationepigeneticsH3K9 methylationhistone demethylationlysine demethylase |
| spellingShingle | Baoyu Chen Yuwen Zhu Junliang Chen Yifei Feng Yifei Feng Yong Xu Yong Xu Activation of TC10-Like Transcription by Lysine Demethylase KDM4B in Colorectal Cancer Cells Frontiers in Cell and Developmental Biology transcriptional regulation epigenetics H3K9 methylation histone demethylation lysine demethylase |
| title | Activation of TC10-Like Transcription by Lysine Demethylase KDM4B in Colorectal Cancer Cells |
| title_full | Activation of TC10-Like Transcription by Lysine Demethylase KDM4B in Colorectal Cancer Cells |
| title_fullStr | Activation of TC10-Like Transcription by Lysine Demethylase KDM4B in Colorectal Cancer Cells |
| title_full_unstemmed | Activation of TC10-Like Transcription by Lysine Demethylase KDM4B in Colorectal Cancer Cells |
| title_short | Activation of TC10-Like Transcription by Lysine Demethylase KDM4B in Colorectal Cancer Cells |
| title_sort | activation of tc10 like transcription by lysine demethylase kdm4b in colorectal cancer cells |
| topic | transcriptional regulation epigenetics H3K9 methylation histone demethylation lysine demethylase |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.617549/full |
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