lnc-β-Catm elicits EZH2-dependent β-catenin stabilization and sustains liver CSC self-renewal,  Nature Structural & Molecular Biology， 23, 631–639 (2016)

Nature Structural & Molecular Biology， 23, 631–639 (2016) doi:10.1038/nsmb.3235

lnc-β-Catm elicits EZH2-dependent β-catenin stabilization and sustains liver CSC self-renewal

Pingping Zhu, Yanying Wang, Guanling Huang, Buqing Ye, Benyu Liu, Jiayi Wu, Ying Du, Lei He & Zusen Fan

Abstract

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-β-Catm, which is highly expressed in human HCC tumors and liver CSCs. We found that lnc-β-Catm is required for self-renewal of liver CSCs and tumor propagation in mice. lnc-β-Catm associates with β-catenin and the methyltransferase EZH2, thereby promoting β-catenin methylation. Methylation suppresses the ubiquitination of β-catenin and promotes its stability, thus leading to activation of Wnt–β-catenin signaling. Accordingly, the expression of lnc-β-Catm, EZH2 and Wnt–β-catenin targets is positively correlated with cancer severity and prognosis of people with HCC.

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文章链接：http://www.nature.com/nsmb/journal/v23/n7/full/nsmb.3235.html