AUTHOR=Chen Baoyu , Zhu Yuwen , Chen Junliang , Feng Yifei , Xu Yong 

TITLE=Activation of TC10-Like Transcription by Lysine Demethylase KDM4B in Colorectal Cancer Cells

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.617549

DOI=10.3389/fcell.2021.617549

ISSN=2296-634X

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 TCL contributes to aggressive migration and invasion in malignant CRC cells. TCL expression is elevated in malignant CRC cells compared to more benign CRC cells 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 ERG1 to the TCL promoter to activate transcription. Mechanistically, KDM4B mediated H3K9 demethylase facilitated the assembly of pre-initiation complex on the TCL promoter. KDM4B knockdown attenuated migration and invasion of CRC cells. Importantly, KDM4B expression was up-regulated 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.