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

doi:10.1002/mc.22764

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

Otolaryngology

Research output: Contribution to journal › Article › peer-review

27 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 language	English (US)
Pages (from-to)	408-418
Number of pages	11
Journal	Molecular Carcinogenesis
Volume	57
Issue number	3
DOIs	https://doi.org/10.1002/mc.22764
State	Published - Mar 2018

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© 2017 Wiley Periodicals, Inc.

Keywords

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

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

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",

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

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year = "2018",

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doi = "10.1002/mc.22764",

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T1 - LncAPC drives Wnt/β-catenin activation and liver TIC self-renewal through EZH2 mediated APC transcriptional inhibition

AU - Fu, Xiaomin

AU - Lin, Jizhen

AU - Qin, Fujun

AU - Yang, Zihe

AU - Ding, Yuechao

AU - Zhang, Yong

AU - Han, Lu

AU - Zhu, Xiaoyan

AU - Zhang, Qinxian

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - Wnt/β-catenin

KW - liver cancer

KW - long noncoding RNA

KW - remodeling complex

KW - tumor initiating cells

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

Abstract

Bibliographical note

Keywords

UN SDGs

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