LncAPC drives Wnt/β-catenin activation and liver TIC self-renewal through EZH2 mediated APC transcriptional inhibition

Xiaomin Fu, Jizhen Lin, Fujun Qin, Zihe Yang, Yuechao Ding, Yong Zhang, Lu Han, Xiaoyan Zhu, Qinxian Zhang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis, and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver cancer and liver TICs. LncAPC was required for liver TIC self-renewal. Silencing and overexpressing lncAPC showed impaired and enhanced sphere formation capacity of liver TICs, respectively. By recruiting EZH2 to APC promoter, LncAPC inhibits APC transcription and thus drives the activation of Wnt/β-catenin signaling. Attenuate binding between EZH2 and APC promoter was observed upon lncAPC knockdown. What is more, lncAPC-EZH2-APC axis can be targeted to eliminate liver TICs. Altogether, LncAPC promotes liver TIC self-renewal through EZH2-dependent APC transcriptional inhibition.

Original languageEnglish (US)
Pages (from-to)408-418
Number of pages11
JournalMolecular Carcinogenesis
Volume57
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • Wnt/β-catenin
  • liver cancer
  • long noncoding RNA
  • remodeling complex
  • tumor initiating cells

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