LncGata6 maintains stemness of intestinal stem cells and promotes intestinal tumorigenesis

被引：109

作者：

Zhu, Pingping ^{[1
]}

Wu, Jiayi ^{[1
,2
]}

Wang, Yanying ^{[1
]}

Zhu, Xiaoxiao ^{[3
]}

Lu, Tiankun ^{[1
,2
]}

Liu, Benyu ^{[1
,2
]}

He, Luyun ^{[1
,2
]}

Ye, Buqing ^{[1
]}

Wang, Shuo ^{[1
]}

Meng, Shu ^{[3
]}

Fan, Dongdong ^{[3
]}

Wang, Jing ^{[1
,2
]}

Yang, Liuliu ^{[1
,2
]}

Qin, Xiwen ^{[1
,2
]}

Du, Ying ^{[1
]}

Li, Chong ^{[1
]}

He, Lei ^{[4
]}

Ren, Weizheng ^{[4
]}

Wu, Xin ^{[5
]}

Tian, Yong ^{[2
,3
]}

Fan, Zusen ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, CAS Key Lab Infect & Immun, Beijing, Peoples R China

[2] Univ Chinese Acad Sci, Beijing, Peoples R China

[3] Chinese Acad Sci, Inst Biophys, CAS Key Lab RNA Biol, Beijing, Peoples R China

[4] Peoples Liberat Army Gen Hosp, Dept Hepatobiliary Surg, Beijing, Peoples R China

[5] Peoples Liberat Army Gen Hosp, Dept Gen Surg, Beijing, Peoples R China

来源：

NATURE CELL BIOLOGY | 2018年 / 20卷 / 10期

基金：

北京市自然科学基金; 中国国家自然科学基金;

关键词：

IN-VITRO EXPANSION; SELF-RENEWAL; GENE-EXPRESSION; COLON-CANCER; TRANSCRIPTION; WNT; ACTIVATION; DIFFERENTIATION; CRYPT; LGR5;

D O I：

10.1038/s41556-018-0194-0

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1134 / +

页数：13

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