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• W3176800440 abstract "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." @default.
• W3176800440 created "2021-07-05" @default.
• W3176800440 creator A5008046219 @default.
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• W3176800440 creator A5039932983 @default.
• W3176800440 creator A5043078772 @default.
• W3176800440 creator A5084914364 @default.
• W3176800440 date "2021-06-23" @default.
• W3176800440 modified "2023-10-15" @default.
• W3176800440 title "Activation of TC10-Like Transcription by Lysine Demethylase KDM4B in Colorectal Cancer Cells" @default.
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• W3176800440 doi "https://doi.org/10.3389/fcell.2021.617549" @default.
• W3176800440 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8260841" @default.
• W3176800440 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34249900" @default.
• W3176800440 hasPublicationYear "2021" @default.
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