Iron elevates mesenchymal and metastatic biomarkers in HepG2 cells

Abstract Liver iron excess is observed in several chronic liver diseases and is associated with the development of hepatocellular carcinoma (HCC). However, apart from oxidative stress, other cellular mechanisms by which excess iron may mediate/increase HCC predisposition/progression are not known. H...

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Autores principales:	Kosha J. Mehta, Paul A. Sharp
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e7272b9f935c4cb39e707efe6166244d
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spelling	oai:doaj.org-article:e7272b9f935c4cb39e707efe6166244d2021-12-02T11:57:57ZIron elevates mesenchymal and metastatic biomarkers in HepG2 cells10.1038/s41598-020-78348-52045-2322https://doaj.org/article/e7272b9f935c4cb39e707efe6166244d2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78348-5https://doaj.org/toc/2045-2322Abstract Liver iron excess is observed in several chronic liver diseases and is associated with the development of hepatocellular carcinoma (HCC). However, apart from oxidative stress, other cellular mechanisms by which excess iron may mediate/increase HCC predisposition/progression are not known. HCC pathology involves epithelial to mesenchymal transition (EMT), the basis of cancer phenotype acquisition. Here, the effect of excess iron (holo-transferrin 0–2 g/L for 24 and 48 h) on EMT biomarkers in the liver-derived HepG2 cells was investigated. Holo-transferrin substantially increased intracellular iron. Unexpectedly, mRNA and protein expression of the epithelial marker E-cadherin either remained unaltered or increased. The mRNA and protein levels of metastasis marker N-cadherin and mesenchymal marker vimentin increased significantly. While the mRNA expression of EMT transcription factors SNAI1 and SNAI2 increased and decreased, respectively after 24 h, both factors increased after 48 h. The mRNA expression of TGF-β (EMT-inducer) showed no significant alterations. In conclusion, data showed direct link between iron and EMT. Iron elevated mesenchymal and metastatic biomarkers in HepG2 cells without concomitant decrement in the epithelial marker E-cadherin and altered the expression of the key EMT-mediating transcription factors. Such studies can help identify molecular targets to devise iron-related adjunctive therapies to ameliorate HCC pathophysiology.Kosha J. MehtaPaul A. SharpNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kosha J. Mehta Paul A. Sharp Iron elevates mesenchymal and metastatic biomarkers in HepG2 cells
description	Abstract Liver iron excess is observed in several chronic liver diseases and is associated with the development of hepatocellular carcinoma (HCC). However, apart from oxidative stress, other cellular mechanisms by which excess iron may mediate/increase HCC predisposition/progression are not known. HCC pathology involves epithelial to mesenchymal transition (EMT), the basis of cancer phenotype acquisition. Here, the effect of excess iron (holo-transferrin 0–2 g/L for 24 and 48 h) on EMT biomarkers in the liver-derived HepG2 cells was investigated. Holo-transferrin substantially increased intracellular iron. Unexpectedly, mRNA and protein expression of the epithelial marker E-cadherin either remained unaltered or increased. The mRNA and protein levels of metastasis marker N-cadherin and mesenchymal marker vimentin increased significantly. While the mRNA expression of EMT transcription factors SNAI1 and SNAI2 increased and decreased, respectively after 24 h, both factors increased after 48 h. The mRNA expression of TGF-β (EMT-inducer) showed no significant alterations. In conclusion, data showed direct link between iron and EMT. Iron elevated mesenchymal and metastatic biomarkers in HepG2 cells without concomitant decrement in the epithelial marker E-cadherin and altered the expression of the key EMT-mediating transcription factors. Such studies can help identify molecular targets to devise iron-related adjunctive therapies to ameliorate HCC pathophysiology.
format	article
author	Kosha J. Mehta Paul A. Sharp
author_facet	Kosha J. Mehta Paul A. Sharp
author_sort	Kosha J. Mehta
title	Iron elevates mesenchymal and metastatic biomarkers in HepG2 cells
title_short	Iron elevates mesenchymal and metastatic biomarkers in HepG2 cells
title_full	Iron elevates mesenchymal and metastatic biomarkers in HepG2 cells
title_fullStr	Iron elevates mesenchymal and metastatic biomarkers in HepG2 cells
title_full_unstemmed	Iron elevates mesenchymal and metastatic biomarkers in HepG2 cells
title_sort	iron elevates mesenchymal and metastatic biomarkers in hepg2 cells
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e7272b9f935c4cb39e707efe6166244d
work_keys_str_mv	AT koshajmehta ironelevatesmesenchymalandmetastaticbiomarkersinhepg2cells AT paulasharp ironelevatesmesenchymalandmetastaticbiomarkersinhepg2cells
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Iron elevates mesenchymal and metastatic biomarkers in HepG2 cells

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