Prolyl-4-Hydroxylase 2 Potentially Contributes to Hepatocellular Carcinoma-Associated Erythrocytosis by Maintaining Hepatocyte Nuclear Factor-4α Expression.
Cell Physiol Biochem
; 37(6): 2257-64, 2015.
Article
em En
| MEDLINE
| ID: mdl-26624507
ABSTRACT
BACKGROUND:
Increased red blood cell count (Erythrocytosis) is an important paraneoplastic syndrome of hepatocellular carcinoma (HCC) and is a significant risk factor for lethal lung artery thromboembolism. HCC-associated erythrocytosis is partially caused by the ability of several HCC cells to produce erythropoietin (EPO). Prolyl-4-hydroxylase 2 (PHD2) is an enzyme encoded by the gene EGLN1. The best-known function of PHD2 is to mediate the oxygen-dependent degradation of the labile α-subunit of hypoxia-inducible factor (HIF). However, there is increasing evidence that PHD2 also regulates HIF-independent pathways by interacting with other substrates.METHODS:
In the EPO-producing human HCC cell line HepG2, the expression of PHD2 gene was silenced with siRNA. EPO production was estimated using quantitative PCR and ELISA.RESULTS:
In HepG2 cells, PHD2 suppresses the activity of TGF-ß1 pathway and consequently maintains the expression of hepatocyte nuclear factor-4α (HNF-4α), an important transcription factor promoting the EPO expression in hepatocytes. PHD2 knockdown caused a marked reduction of EPO production. HIF seemed not to be involved in this biology.CONCLUSION:
Our findings show that PHD2 represents a potential contributing factor for HCC-associated erythrocytosis. Selective inhibition of PHD2 in HCC cells might be considered as a new way to manage erythrocytosis in HCC patients.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Policitemia
/
Eritropoetina
/
Carcinoma Hepatocelular
/
Fator 4 Nuclear de Hepatócito
/
Prolil Hidroxilases
/
Neoplasias Hepáticas
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Physiol Biochem
Assunto da revista:
BIOQUIMICA
/
FARMACOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article