Functional diversity of TMPRSS6 isoforms and variants expressed in hepatocellular carcinoma cell lines
| Autor: | Sébastien P. Dion, Rafael Najmanovich, François Béliveau, Richard Leduc, Louis-Philippe Morency, Antoine Désilets |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gene isoform TMPRSS6 Carcinoma Hepatocellular Iron Mutant lcsh:Medicine Article 03 medical and health sciences Hepcidin Humans Protein Isoforms lcsh:Science Regulation of gene expression Multidisciplinary Anemia Iron-Deficiency biology Liver cell Liver Neoplasms Serine Endopeptidases lcsh:R Membrane Proteins Hep G2 Cells Molecular biology Gene Expression Regulation Neoplastic 030104 developmental biology Cell culture Mutation biology.protein lcsh:Q HAMP |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-9 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-30618-z |
| Popis: | TMPRSS6, also known as matriptase-2, is a type II transmembrane serine protease that plays a major role in iron homeostasis by acting as a negative regulator of hepcidin production through cleavage of the BMP co-receptor haemojuvelin. Iron-refractory iron deficiency anaemia (IRIDA), an iron metabolism disorder, is associated with mutations in the TMPRSS6 gene. By analysing RNA-seq data encoding TMPRSS6 isoforms and other proteins involved in hepcidin production, we uncovered significant differences in expression levels between hepatocellular carcinoma (HCC) cell lines and normal human liver samples. Most notably, TMPRSS6 and HAMP expression was found to be much lower in HepG2 and Huh7 cells when compared to human liver samples. Furthermore, we characterized the common TMPRSS6 polymorphism V736A identified in Hep3B cells, the V795I mutation found in HepG2 cells, also associated with IRIDA, and the G603R substitution recently detected in two IRIDA patients. While variant V736A is as active as wild-type TMPRSS6, mutants V795I and G603R displayed significantly reduced proteolytic activity. Our results provide important information about commonly used liver cell models and shed light on the impact of two TMPRSS6 mutations associated with IRIDA. |
| Databáze: | OpenAIRE |
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