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Cited by 25Cancer Cells and MetastasisHepatocellular Carcinoma Treatment and PrognosisEpigenetics and DNA Methylation

Hepatic ARID3A facilitates liver cancer malignancy by cooperating with CEP131 to regulate an embryonic stem cell-like gene signature

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Shen, Mengting, Li, Shengli, Zhao, Yiming, Liu, Yizhe, Liu, Zhen, Huan, Lin, Qiao, Yejun, Wang, Lu +3 more·2022·Cell Death & Disease
DOI 10.1038/s41419-022-05187-9PMC PMC9411159
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Abstract

Liver cancer stemness refers to the stem cell-like phenotype of hepatocarcinoma cells and is closely related to a high degree of tumour malignancy. Here, we identified AT-rich interacting domain 3A (ARID3A) as one of the most upregulated stemness-related transcription factors in liver cancer by an in vitro functional screen. ARID3A can promote liver cancer cell viability and metastasis both in vitro and in vivo. Mechanistically, ARID3A interacts with CEP131 and transcriptionally activates KDM3A by co-occupying its promoter element, further upregulating the expression of downstream embryonic stem (ES) signature genes via demethylation of H3K9me2. ARID3A and CEP131 promote an ES cell gene signature through activation of KDM3A and contribute to the poor prognosis of liver cancer patients. Collectively, these results provide evidence highlighting a transcription-dependent mechanism of ARID3A in stemness regulation in liver cancer. The ARID3A/CEP131-KDM3A regulatory circuit could serve as a prognostic indicator and potential therapeutic target for liver cancer.

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Cited by

Sorted by citations

Authors
Shen, M., Li, S., Zhao, Y., Liu, Y., Liu, Z., Huan, L., Qiao, Y., Wang, L., Han, L., Chen, Z., & He, X.
Affiliations
  • Shanghai Medical College of Fudan University (CN)
  • Shanghai Jiao Tong University (CN)
  • Fudan University (CN)
  • Texas A&M University (US)
Corresponding author
  • Wang, Lu
  • Han, Leng
  • Chen, Zhiao
  • He, Xianghuo
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2022-08-25
Volume
13
Issue
8
Pages
732-732
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/s41419-022-05187-9
PMC
PMC9411159
OpenAlex
W4293222301
Cited by
25
References
1
Citations by year
2026: 5 · 2025: 10 · 2024: 5 · 2023: 4 · 2022: 1
FWCI
2.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81972247, 82172937, 81930123, 81790252)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
ARID3A, KDM3A, hepatocellular carcinoma, H3K9 demethylation, metastasis, tumor malignancy, prognostic factors, therapeutic target
MeSH terms
Cytoskeletal Proteins, DNA-Binding Proteins, Humans, Liver Neoplasms, Promoter Regions, Genetic, Transcription Factors, Cell Cycle Proteins, Embryonic Stem Cells, Jumonji Domain-Containing Histone Demethylases

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