Sasaki Katsunori, Kohgo Yutaka, Ohtake Takaaki
Division of Gastroenterological Surgery II, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Department of Gastroenterology, International University of Health and Welfare Hospital, Nasushiobara, Japan.
Vitam Horm. 2019;110:131-141. doi: 10.1016/bs.vh.2019.01.006. Epub 2019 Feb 8.
Hepcidin is a main regulator of iron metabolism, of which abnormal expression affects intestinal absorption and reticuloendothelial sequestration of iron by interacting with ferroportin. It is also noted that abnormal iron accumulation is one of the key factors to facilitate promotion and progression of cancer including hepatoma. In this study, we firstly revealed that a new alternative HAMP transcript was found in hepatoma-derived cell line HLF, which was identical to the wild-type preprohepcidin sequence except lacking of an internal 60 bases. In addition to HLF, most of hepatoma-derived cell lines have significant copy numbers of variant-type hepcidin mRNA by a copy-based-digital PCR. Furthermore, the copy number of hepcidin mRNA variant was significantly higher in serum exosomes of hepatocellular carcinoma patients. The quantification of exosomal hepcidin mRNA variant may serve as a potential new biomarker for HCC diagnosis.
铁调素是铁代谢的主要调节因子，其异常表达通过与铁转运蛋白相互作用影响肠道对铁的吸收和网状内皮系统对铁的扣押。还应注意的是，铁的异常蓄积是促进包括肝癌在内的癌症发生和发展的关键因素之一。在本研究中，我们首先揭示在肝癌来源的细胞系HLF中发现了一种新的可变HAMP转录本，它与野生型前体铁调素序列相同，只是缺少内部60个碱基。除HLF外，大多数肝癌来源的细胞系通过基于拷贝数的数字PCR检测到有显著拷贝数的变异型铁调素mRNA。此外，肝细胞癌患者血清外泌体中铁调素mRNA变异体的拷贝数显著更高。外泌体铁调素mRNA变异体的定量分析可能成为肝癌诊断的一种潜在新生物标志物。
