Hepcidin in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common reasons for cancer-related deaths. Excess iron increases HCC risk. Inevitably, hepcidin, the iron hormone that maintains systemic iron homoeostasis is involved in HCC pathology. Distinct from other cancers that show high hepcidin expression, HCC patients can show low hepcidin levels. Thus, it is of immense clinical benefit to address the regulation and action of hepcidin in HCC as this may help in identifying molecular targets for diagnosis, prognosis, and therapeutics. Accordingly, this review explores hepcidin in HCC. It presents the levels of tissue and serum hepcidin and explains the mechanisms that contribute to hepcidin reduction in HCC. These include downregulation of HAMP, TfR2, HJV, ALK2 and circular RNA circ_0004913, upregulation of matriptase-2 and GDF15, inactivation of RUNX3 and mutation in TP53. The enigmas around mir-122 and the functionalities of two major hepcidin inducers BMP6 and IL6 in relation to hepcidin in HCC are discussed. Effects of hepcidin downregulation are explained, specifically, increased cancer proliferation via activation of CDK1/STAT3 pathway and increased HCC risk due to reduction in a hepcidin-mediated protective effect against hepatic stellate cell activation. Hepcidin–ferroportin axis in HCC is addressed. Finally, the role of hepcidin in the diagnosis, prognosis and therapeutics of HCC is highlighted.

Iron Depletion in Systemic and Muscle Compartments Defines a Specific Phenotype of Severe COPD in Female and Male Patients: Implications in Exercise Tolerance

“…Hepcidin is a peptide hormone that play an important role in the systemic iron regulation through its interaction with the major iron export protein, the ferroportin [ 12 , 14 ]. In patients with chronic diseases such as chronic hepatitis C, hepatocellular carcinoma, and inflammatory bowel disease, levels of hepcidin were significantly reduced compared to control subjects [ 47 , 48 , 49 ]. In COPD patients with normal iron metabolism, levels of hepcidin were also reduced [ 50 , 51 ].…”

Hepcidin is upregulated and is a potential therapeutic target associated with immunity in glioma

“…Increased expression of hepcidin also represents a risk factor for these tumors. However, hepcidin expression is significantly decreased in liver cancer ( 24 , 25 ). Downregulated expression of hepcidin is closely correlated with liver cancer aggressiveness, immune cell infiltration and worse survival outcomes of patients with liver cancer ( 25 ).…”

Iron and iron-related proteins in alcohol consumers: cellular and clinical aspects

“…Alcoholic cirrhosis patients with low levels of hepcidin show a high risk of hepatocellular carcinoma and death. In this group, low levels of hepcidin associate with poor long-term survival [29,32].…”

“…Thus, when systemic iron loading occurs, hepcidin secretion by the liver is increased. Hepcidin prevents iron entry into the circulation by inhibiting intestinal iron absorption and by preventing the release of iron from ironstoring/iron recycling cells in the body [26][27][28][29][30].…”