Iron elevates mesenchymal and metastatic biomarkers in HepG2 cells

• Published in: Scientific reports Vol. 10; no. 1; pp. 21926 - 10
• Main Authors: Mehta, Kosha J., Sharp, Paul A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.12.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 631/337; 631/45; 631/80; Biomarkers; Biomarkers, Tumor - metabolism; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; E-cadherin; Epithelial-Mesenchymal Transition; Gene expression; Hep G2 Cells; Hepatocellular carcinoma; Hepatocytes; Humanities and Social Sciences; Humans; Iron; Iron - metabolism; Liver cancer; Liver diseases; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Mesenchyme; Metastases; Metastasis; multidisciplinary; N-Cadherin; Neoplasm Metastasis; Neoplasm Proteins - metabolism; Oxidative stress; Phenotypes; Science; Science (multidisciplinary); Snail protein; Transcription factors; Transferrins; Vimentin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-78348-5

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.