| Literature DB >> 30224759 |
Pingping Zhu1, Jiayi Wu1,2, Yanying Wang1, Xiaoxiao Zhu3, Tiankun Lu1,2, Benyu Liu1,2, Luyun He1,2, Buqing Ye1, Shuo Wang1, Shu Meng3, Dongdong Fan3, Jing Wang1,2, Liuliu Yang1,2, Xiwen Qin1,2, Ying Du1, Chong Li1, Lei He4, Weizheng Ren4, Xin Wu5, Yong Tian6,7, Zusen Fan8,9.
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.Entities:
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Year: 2018 PMID： 30224759 DOI： 10.1038/s41556-018-0194-0
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824