Progress on epigenetic regulation of iron homeostasis / 浙江大学学报·医学版

Iron homeostasis plays an important role for the maintenance of human health. It is known that iron metabolism is tightly regulated by several key genes, including divalent metal transport-1(), transferrin receptor 1(), transferrin receptor 2(), ferroportin(), hepcidin(), hemojuvelin() and . Recently, it is reported that DNA methylation, histone acetylation, and microRNA (miRNA) epigenetically regulated iron homeostasis. Among these epigenetic regulators, DNA hypermethylation of the promoter region of , and bone morphogenetic protein 6 () genes result in inhibitory effect on the expression of these iron-related gene. In addition, histone deacetylase (HADC) suppresses gene expression. On the contrary, HADC inhibitor upregulates gene expression. Additional reports showed that miRNA can also modulate iron absorption, transport, storage and utilization via downregulation of and other genes. It is noteworthy that some key epigenetic regulatory enzymes, such as DNA demethylase TET2 and histone lysine demethylase JmjC KDMs, require iron for the enzymatic activities. In this review, we summarize the recent progress of DNA methylation, histone acetylation and miRNA in regulating iron metabolism and also discuss the future research directions.

The role of ferroptosis in chronic diseases / 浙江大学学报·医学版

Recently, ferroptosis, an iron-dependent novel type of cell death, has been characterized as an excessive accumulation of lipid peroxides and reactive oxygen species. Emerging studies demonstrate that ferroptosis not only plays an important role in the pathogenesis and progression of chronic diseases, but also functions differently in the different disease context. Notably, it is shown that activation of ferroptosis could potently inhibit tumor growth and increase sensitivity to chemotherapy and immunotherapy in various cancer settings. As a result, the development of more efficacious ferroptosis agonists remains the mainstay of ferroptosis-targeting strategy for cancer therapeutics. By contrast, in non-cancerous chronic diseases, including cardiovascular & cerebrovascular diseases and neurodegenerative diseases, ferroptosis functions as a risk factor to promote these diseases progression through triggering or accelerating tissue injury. As a matter of fact, blocking ferroptosis has been demonstrated to effectively prevent ischemia-reperfusion heart disease in preclinical animal models. Therefore, it is a promising field to develope potent ferroptosis inhibitors for preventing and treating cardiovascular & cerebrovascular diseases and neurodegenerative diseases. In this article, we summarize the most recent progress on ferroptosis in chronic diseases, and draw attention to the possible clinical impact of this recently emerged ferroptosis modalities.