Journal
NATURE CELL BIOLOGY
Volume 20, Issue 10, Pages 1134-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41556-018-0194-0
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Funding
- National Natural Science Foundation of China [91640203, 31530093, 81330047, 31771638, 81672897, 81672956, 81472413, 81572433, 81772646, 31601189]
- Strategic Priority Research Programs of the Chinese Academy of Sciences [XDA12020219, XDB19030203]
- Beijing Natural Science Foundation [7181006, 7162125]
- Postdoctoral Innovative Talent Support Program
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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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