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Mol Carcinog. 2018 Mar;57(3):408-418. doi: 10.1002/mc.22764. Epub 2017 Dec 15.

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

Author information

1
Department of Histology and Embryology, College of Basic Medicine, Zhengzhou University, Henan, China.
2
Department of Cancer Biology Immunotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou University, Henan, China.
3
Department of Otolaryngology, Medical School, University of Minnesota, Twin Cities Campus, Minneapolis, Minnesota.
4
Department of Pathology, School of Medicine, University of Virginia, Virginia.
5
Department of Nuclear Medicine, The Affiliated Beijing Anzhen Hospital of Capital Medical University, Capital Medical University, Beijing, China.
6
Department of Hepatopancreatobiliary Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou University, Henan, China.

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.

KEYWORDS:

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

PMID:
29144570
DOI:
10.1002/mc.22764
[Indexed for MEDLINE]

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