Joachim Jonathan H, Mehta Kosha J
GKT School of Medical Education, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Centre for Education, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Br J Cancer. 2022 Jul;127(2):185-192. doi: 10.1038/s41416-022-01753-2. Epub 2022 Mar 9.
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.
肝细胞癌（HCC）是癌症相关死亡的最常见原因之一。铁过载会增加患HCC的风险。不可避免地，维持全身铁稳态的铁调节激素铁调素参与了HCC的病理过程。与其他铁调素高表达的癌症不同，HCC患者的铁调素水平可能较低。因此，研究铁调素在HCC中的调节和作用具有巨大的临床意义，因为这可能有助于确定诊断、预后和治疗的分子靶点。因此，本综述探讨了铁调素在HCC中的作用。它介绍了组织和血清中铁调素的水平，并解释了导致HCC中铁调素减少的机制。这些机制包括HAMP、TfR2、HJV、ALK2和环状RNA circ_0004913的下调，matriptase-2和GDF15的上调，RUNX3的失活以及TP53的突变。讨论了围绕mir-122的谜团以及两种主要铁调素诱导剂BMP6和IL6在HCC中与铁调素相关的功能。解释了铁调素下调的影响，特别是通过激活CDK1/STAT3途径增加癌症增殖，以及由于铁调素介导的对肝星状细胞激活的保护作用降低而增加HCC风险。探讨了HCC中的铁调素-铁转运蛋白轴。最后，强调了铁调素在HCC诊断、预后和治疗中的作用。
