ABSTRACT. MicroRNA-200 family members are expressed in the developing mouse inner ear and in zebrafish (Danio rerio) olfactory epithelia, taste buds, and neuromasts, and have also been shown to be associated with differentiation of olfactory and taste buds. However, the role of the miR-200 family in the inner ear of zebrafish had not been studied. We investigated the expression and function of the miR-200 family in the zebrafish inner ear via in situ hybridization and loss-of-function methods. Expression of the miR-200 family was weak and dispersed throughout the developing zebrafish inner ear. After knockdown of miR-200 family members in the developing inner ear, no significant differences in development were observed compared to the controls. Otic vesicles, otoliths, and semicircular canals appeared normal. Compared with less differentiated olfactory filaments in olfactory epithelia, the development of hair cells and statoacoustic ganglion neurons were normal. The kinocilia and stereocilia of hair cells, the innervation of hair cells, and the formation of ribbon synapses were also unaffected. Overall, we conclude that the miR-200 family has a negligible role in the development of zebrafish inner ear; the functions of the miR-200 family may be organ-specific.

Ferroptosis is a form of programmed cell death characterized by elevated intracellular ferrous ion levels and increased lipid peroxidation. Since its discovery and characterization in 2012, considerable progress has been made in understanding the regulatory mechanisms and pathophysiological functions of ferroptosis. Recent findings suggest that numerous organ injuries (e.g., ischemia/reperfusion injury) and degenerative pathologies (e.g., aortic dissection and neurodegenerative disease) are driven by ferroptosis. Conversely, insufficient ferroptosis has been linked to tumorigenesis. Furthermore, a recent study revealed the effect of ferroptosis on hematopoietic stem cells under physiological conditions. The regulatory mechanisms of ferroptosis identified to date include mainly iron metabolism, such as iron transport and ferritinophagy, and redox systems, such as glutathione peroxidase 4 (GPX4)-glutathione (GSH), ferroptosis-suppressor-protein 1 (FSP1)-CoQ10, FSP1-vitamin K (VK), dihydroorotate dehydrogenase (DHODH)-CoQ, and GTP cyclohydrolase 1 (GCH1)-tetrahydrobiopterin (BH4). Recently, an increasing number of studies have demonstrated the important regulatory role played by epigenetic mechanisms, especially DNA, RNA, and protein methylation, in ferroptosis. In this review, we provide a critical analysis of the molecular mechanisms and regulatory networks of ferroptosis identified to date, with a focus on the regulatory role of DNA, RNA, and protein methylation. Furthermore, we discuss some debated findings and unanswered questions that should be the foci of future research in this field.