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TAp73β Can Promote Hepatocellular Carcinoma Dedifferentiation

Iscan, Evin ; Ekin, Umut ; Yildiz, Gokhan ; Oz, Ozden ; Keles, Umur LU ; Suner, Aslı ; Cakan-Akdogan, Gulcin ; Ozhan, Gunes ; Nekulova, Marta and Vojtesek, Borivoj , et al. (2021) In Cancers 13(4).
Abstract

Hepatocyte dedifferentiation is a major source of hepatocellular carcinoma (HCC), but its mechanisms are unknown. We explored the p73 expression in HCC tumors and studied the effects of transcriptionally active p73β (TAp73β) in HCC cells. Expression profiles of p73 and patient clinical data were collected from the Genomic Data Commons (GDC) data portal and the TSVdb database, respectively. Global gene expression profiles were determined by pan-genomic 54K microarrays. The Gene Set Enrichment Analysis method was used to identify TAp73β-regulated gene sets. The effects of TAp73 isoforms were analyzed in monolayer cell culture, 3D-cell culture and xenograft models in zebrafish using western blot, flow cytometry, fluorescence imaging,... (More)

Hepatocyte dedifferentiation is a major source of hepatocellular carcinoma (HCC), but its mechanisms are unknown. We explored the p73 expression in HCC tumors and studied the effects of transcriptionally active p73β (TAp73β) in HCC cells. Expression profiles of p73 and patient clinical data were collected from the Genomic Data Commons (GDC) data portal and the TSVdb database, respectively. Global gene expression profiles were determined by pan-genomic 54K microarrays. The Gene Set Enrichment Analysis method was used to identify TAp73β-regulated gene sets. The effects of TAp73 isoforms were analyzed in monolayer cell culture, 3D-cell culture and xenograft models in zebrafish using western blot, flow cytometry, fluorescence imaging, real-time polymerase chain reaction (RT-PCR), immunohistochemistry and morphological examination. TAp73 isoforms were significantly upregulated in HCC, and high p73 expression correlated with poor patient survival. The induced expression of TAp73β caused landscape expression changes in genes involved in growth signaling, cell cycle, stress response, immunity, metabolism and development. Hep3B cells overexpressing TAp73β had lost hepatocyte lineage biomarkers including ALB, CYP3A4, AFP, HNF4α. In contrast, TAp73β upregulated genes promoting cholangiocyte lineage such as YAP, JAG1 and ZO-1, accompanied with an increase in metastatic ability. Our findings suggest that TAp73β may promote malignant dedifferentiation of HCC cells.

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publishing date
type
Contribution to journal
publication status
published
in
Cancers
volume
13
issue
4
publisher
MDPI AG
external identifiers
  • scopus:85100764450
  • pmid:33668566
ISSN
2072-6694
DOI
10.3390/cancers13040783
language
English
LU publication?
no
id
760727fc-0c8b-4b1b-a697-40c7fc20962c
date added to LUP
2022-12-28 10:09:28
date last changed
2024-06-13 10:00:55
@article{760727fc-0c8b-4b1b-a697-40c7fc20962c,
  abstract     = {{<p>Hepatocyte dedifferentiation is a major source of hepatocellular carcinoma (HCC), but its mechanisms are unknown. We explored the p73 expression in HCC tumors and studied the effects of transcriptionally active p73β (TAp73β) in HCC cells. Expression profiles of p73 and patient clinical data were collected from the Genomic Data Commons (GDC) data portal and the TSVdb database, respectively. Global gene expression profiles were determined by pan-genomic 54K microarrays. The Gene Set Enrichment Analysis method was used to identify TAp73β-regulated gene sets. The effects of TAp73 isoforms were analyzed in monolayer cell culture, 3D-cell culture and xenograft models in zebrafish using western blot, flow cytometry, fluorescence imaging, real-time polymerase chain reaction (RT-PCR), immunohistochemistry and morphological examination. TAp73 isoforms were significantly upregulated in HCC, and high p73 expression correlated with poor patient survival. The induced expression of TAp73β caused landscape expression changes in genes involved in growth signaling, cell cycle, stress response, immunity, metabolism and development. Hep3B cells overexpressing TAp73β had lost hepatocyte lineage biomarkers including ALB, CYP3A4, AFP, HNF4α. In contrast, TAp73β upregulated genes promoting cholangiocyte lineage such as YAP, JAG1 and ZO-1, accompanied with an increase in metastatic ability. Our findings suggest that TAp73β may promote malignant dedifferentiation of HCC cells.</p>}},
  author       = {{Iscan, Evin and Ekin, Umut and Yildiz, Gokhan and Oz, Ozden and Keles, Umur and Suner, Aslı and Cakan-Akdogan, Gulcin and Ozhan, Gunes and Nekulova, Marta and Vojtesek, Borivoj and Uzuner, Hamdiye and Karakülah, Gökhan and Alotaibi, Hani and Ozturk, Mehmet}},
  issn         = {{2072-6694}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{4}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{TAp73β Can Promote Hepatocellular Carcinoma Dedifferentiation}},
  url          = {{http://dx.doi.org/10.3390/cancers13040783}},
  doi          = {{10.3390/cancers13040783}},
  volume       = {{13}},
  year         = {{2021}},
}