Inhibition of Arid1a increases stem/progenitor cell-like properties of liver cancer

ARID1A, a key subunit of the SWI/SNF chromatin remodeling complex, exhibits recurrent mutations in various types of human cancers, including liver cancer. However, the function of ARID1A in the pathogenesis of liver cancer remains controversial. Here, we demonstrate that Arid1a knockout may result i...

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Bibliographic Details
Published in:Cancer letters 2022-10, Vol.546, p.215869-215869, Article 215869
Main Authors: Wang, Lan, Deng, Chuan-Huai, Luo, Qing, Su, Xian-Bin, Shang, Xue-Ying, Song, Shu-Jin, Cheng, Sheng, Qu, Yu-Lan, Zou, Xin, Shi, Yi, Wang, Qian, Du, Shi-Chun, Han, Ze-Guang
Format: Article
Language:English
Subjects:
Cancer stem cell
Cell differentiation
Cell self-renewal
Chromatin accessibility
Chromatin remodeling
Hepatocytes
Kinases
Laboratories
Liver cancer
Progenitor cells
scRNA-seq
Stem cells
SWI/SNF chromatin remodeling complex
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Summary:ARID1A, a key subunit of the SWI/SNF chromatin remodeling complex, exhibits recurrent mutations in various types of human cancers, including liver cancer. However, the function of ARID1A in the pathogenesis of liver cancer remains controversial. Here, we demonstrate that Arid1a knockout may result in states of different cell differentiation, as indicated by single-cell RNA sequencing (scRNA-seq) analysis. Bulk RNA-seq also revealed that Arid1a deficiency upregulated these genes related to cell stemness and differentiation, but downregulated genes related to the hepatic functions. Furthermore, we confirmed that deficiency of Arid1a increased the expression of hepatic stem/progenitor cell markers, such as Cd133 and Epcam, and enhanced the self-renewal ability of cells. Mechanistic studies revealed that Arid1a loss remodeled the chromatin accessibility of some genes related to liver functions. Thus, Arid1a deficiency might contribute to cancer development by increasing the number of stem/progenitor-like cells through dysregulating the expression of these genes related to cell stemness, differentiation and liver functions. •Loss of Arid1a results in different cell differentiation states.•Arid1a deficiency increases the stem/progenitor features of liver cancer cells.•Arid1a loss changes chromatin accessibility to alter genes related to liver function.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2022.215869