Journal
CELL STEM CELL
Volume 16, Issue 4, Pages 413-425Publisher
CELL PRESS
DOI: 10.1016/j.stem.2015.03.003
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Funding
- National Natural Science Foundation of China [81330047, 91419308, 81402459, 81272270, 81101531]
- State Projects of Essential Drug Research and development [2012ZX09103301-041]
- 973 Program of the MOST of China [2015CB553705, 2010CB911902]
- Strategic Priority Research Programs of the Chinese Academy of Sciences [XDA01010407]
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Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer, and it is characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanisms underlying their self-renewal and maintenance are poorly understood. Here, using transcriptome microarray analysis, we identified a long noncoding RNA (IncRNA) termed IncTCF7 that is highly expressed in HCC tumors and liver CSCs. LncTCF7 is required for liver CSC self-renewal and tumor propagation. Mechanistically, IncTCF7 recruits the SWI/SNF complex to the promoter of TCF7 to regulate its expression, leading to activation of Wnt signaling. Our data suggest that IncTCF7-mediated Wnt signaling primes liver CSC self-renewal and tumor propagation. In sum, therefore, we have identified an IncRNA-based Wnt signaling regulatory circuit that promotes tumorigenic activity in liver cancer stem cells, highlighting the role that IncRNAs can play in tumor growth and propagation.
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