LncGata6 maintains stemness of intestinal stem cells and promotes intestinal tumorigenesis

Nature Cell Biology
Pingping ZhuZusen Fan

Abstract

The intestinal epithelium harbours remarkable self-renewal capacity that is driven by Lgr5+ intestinal stem cells (ISCs) at the crypt base. However, the molecular mechanism controlling Lgr5+ ISC stemness is incompletely understood. We show that a Gata6 long noncoding RNA (lncGata6) is highly expressed in ISCs. LncGata6 knockout or conditional knockout in ISCs impairs the stemness of ISCs and epithelial regeneration. Mechanistically, lncGata6 recruits the NURF complex onto the Ehf promoter to induce its transcription, which promotes the expression of Lgr4/5 to enhance Wnt signalling activation. Moreover, the human orthologue lncGATA6 is highly expressed in the cancer stem cells of colorectal cancer and promotes tumour initiation and progression. Antisense oligonucleotides against lncGATA6 exhibit strong therapeutic efficacy on colorectal cancer. Thus, targeting lncGATA6 will have potential clinical applications in colorectal cancer treatment as an ideal therapeutic target.

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Citations

May 17, 2019·Cancer Biology & Therapy·Ruishuang MaHulun Li
Jul 14, 2019·Journal of Experimental & Clinical Cancer Research : CR·Ang ZhengFeng Jin
May 3, 2019·American Journal of Physiology. Cell Physiology·Lan XiaoJian-Ying Wang
Aug 11, 2020·Journal of Experimental & Clinical Cancer Research : CR·Qing HanZhiwang Song
Sep 2, 2020·Journal of Translational Medicine·Xiaoying LiFeng Jin
Sep 24, 2019·Journal of Cellular Physiology·Hung-Tzi LaiYeu Su
Aug 9, 2019·Animal Models and Experimental Medicine·Fei ZhangYong Tian
Nov 19, 2019·Journal of Cellular and Molecular Medicine·Xinyue SongMinjie Wei
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Sep 17, 2020·International Journal of Molecular Sciences·Athina A KyriaziStavroula Baritaki
Oct 21, 2020·Biological Trace Element Research·Chunlin YuYiping Liu
Jan 1, 2020·RNA Biology·Yan HuangXiangting Wang
Oct 16, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christiane E Olivero, Nadya Dimitrova
Apr 27, 2021·Journal of Cellular Physiology·Vipin K YadavJalaj Gupta
Jan 29, 2021·Journal of Molecular Cell Biology·Wei ShaoYi-Zheng Wang
Aug 10, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiaoting LinFeng Ye
Jan 2, 2021·Cell Regeneration·Guoli ZhuRongwen Xi
Nov 6, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yanan LiZi Wang

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Methods Mentioned

BETA
fluorescence-activated cell sorting
PCR
FACS
antisense purification
RAP
immunoprecipitation
in
pulldown
in vitro transcription
ChIRP

Software Mentioned

FlowJo
TOPFLash
Adobe Photoshop CC
Treestar
ImageJ
Excel

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