Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 23, Issue 7, Pages 631-639Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3235
Keywords
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Funding
- National Natural Science Foundation of China [91419308, 31530093, 81330047, 81402459]
- State Projects of Essential Drug Research and Development [2012ZX09103301-041]
- 973 Program of the MOST of China [2015CB553705]
- Strategic Priority Research Programs of the Chinese Academy of Sciences [XDA01010407]
- Beijing Natural Science Foundation [7162125]
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Liver cancer stem cells (CSCs) may contribute to the high rate of recurrence and heterogeneity of hepatocellular carcinoma (HCC); however, the molecular mechanisms underlying their self-renewal and differentiation remain largely unknown. Through analysis of transcriptome microarray data, we identified a long noncoding RNA (lncRNA) called lnc-beta-Catm, which is highly expressed in human HCC tumors and liver CSCs. We found that lnc-beta-Catm is required for self-renewal of liver CSCs and tumor propagation in mice. lnc-beta-Catm associates with beta-catenin and the methyltransferase EZH2, thereby promoting beta-catenin methylation. Methylation suppresses the ubiquitination of beta-catenin and promotes its stability, thus leading to activation of Wnt-beta-catenin signaling. Accordingly, the expression of lnc-beta-Catm, EZH2 and Wnt-beta-catenin targets is positively correlated with cancer severity and prognosis of people with HCC.
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