Lnc-β-Catm Elicits EZH2-dependent β-catenin Stabilization and Sustains Liver CSC Self-renewal

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2016 May 31

PMID 27239797

Citations 135

Authors

Pingping Zhu

Yanying Wang

Guanling Huang

Buqing Ye

Benyu Liu

Jiayi Wu

Ying Du

Lei He

Zusen Fan

Affiliations

Soon will be listed here.

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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