Ferroptosis is a regulated form of cell death driven by small molecules or conditions that induce lipid-based reactive oxygen species (ROS) accumulation. This form of iron-dependent cell death is morphologically and genetically distinct from apoptosis, necroptosis, and autophagy. miRNAs are known to play crucial roles in diverse fundamental biological processes. However, to date no study has reported miRNA-mediated regulation of ferroptosis. Here we show that miR-137 negatively regulates ferroptosis by directly targeting glutamine transporter SLC1A5 in melanoma cells. Ectopic expression of miR-137 suppressed SLC1A5, resulting in decreased glutamine uptake and malondialdehyde (MDA) accumulation. Meanwhile, antagomir-mediated inactivation of endogenous miR-137 increased the sensitivity of melanoma cells to erastin- and RSL3-induced ferroptosis. Importantly, knockdown of miR-137 increased the antitumor activity of erastin by enhancing ferroptosis both in vitro and in vivo. Collectively, these data indicate that miR-137 plays a novel and indispensable role in ferroptosis by inhibiting glutaminolysis and suggest a potential therapeutic approach for melanoma.

Ferroptosis is a newly defined form of regulated cell death characterized by the irondependent accumulation of lipid hydroperoxides. Erastin, the ferroptosis activator, binds to voltage-dependent anion channels VDAC2 and VDCA3, but treatment with erastin can result in the degradation of the channels. Here, the authors show that Nedd4 is induced following erastin treatment, which leads to the ubiquitination and subsequent degradation of the channels. Depletion of Nedd4 limits the protein degradation of VDAC2/3, which increases the sensitivity of cancer cells to erastin. By understanding the molecular mechanism of erastin-induced cellular resistance, we can discover how cells adapt to new molecules to maintain homeostasis. Furthermore, erastin-induced resistance mediated by FOXM1-Nedd4-VDAC2/3 negative feedback loop provides an initial framework for creating avenues to overcome the drug resistance of ferroptosis activators.

Ferroptosis is a recently recognized form of regulated cell death driven by lipid-based reactive oxygen species (ROS) accumulation. However, the molecular mechanisms of ferroptosis regulation are still largely unknown. Here we identified a novel miRNA, miR-9, as an important regulator of ferroptosis by directly targeting GOT1 in melanoma cells. Overexpression of miR-9 suppressed GOT1 by directly binding to its 3'-UTR, which subsequently reduced erastin- and RSL3-induced ferroptosis. Conversely, suppression of miR-9 increased the sensitivity of melanoma cells to erastin and RSL3. Importantly, anti-miR-9 mediated lipid ROS accumulation and ferroptotic cell death could be abrogated by inhibiting glutaminolysis process. Taken together, our findings demonstrate that miR-9 regulates ferroptosis by targeting GOT1 in melanoma cells, illustrating the important role of miRNA in ferroptosis.

We have examined the Raman spectra of violet and infrared emitting Ge+-implanted SiO2 films with special emphasis upon annealing temperature (AT) dependence of Raman scattering. We found that the complete spectrum mainly consists of three bands at 220–280, 300, and 430 cm−1, corresponding to scattering of Ge-related components, Ge nanocrystallites, and localized Si–Si optical phonons in the Ge neighborhoods, respectively. The Ge crystalline band shows an obvious AT dependence. The theoretical result from the phonon confinement model can predict its linewidth change with AT, but cannot explain its constant peak frequency. Based on the experimental result from x-ray diffraction, we attributed the discrepancy mainly to the compressive stress exerted on Ge nanocrystallites, which leads to the upshift of Ge crystallite peak thereby basically compensating the downshift caused by the confinement on phonon frequency.

SiO 2 films with Ge+ implantation at an energy of 60 keV and a dose of 1×1016 cm−2, followed by annealing at different temperature, exhibit a broad infrared photoluminescence (PL) at room temperature under an excitation of the 514.5 nm line of Ar+ laser. With increasing the annealing temperature, the intensity of the infrared PL band decreases, its full width at half maximum increases, and its energy redshifts. Spectral analysis and some experimental results from Raman scattering, electron spin resonance, and infrared spectroscopy strongly suggest that the infrared PL is mainly related to interfacial oxygen-deficient-type defects between the oxide and Ge nanocrystals.

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Three photoluminescence (PL) bands at 340–370, 400–430, and 740 nm were observed at room temperature in a-Si:H:O films fabricated by plasma enhanced chemical vapor deposition without any postprocessing. The violet-blue emission is very strong and stable, and its intensity is closely related to the oxygen content in the films, which can be controlled by the applied dc biases on the sample substrates during deposition. The first two PL peaks are ascribed to Si–O related species, and the last one to the quantum size effect of the nanocrystallites embedded in the a-Si:H:O matrix.

The rapid occurrence of emerging infectious diseases demonstrates an urgent need for a new preclinical experimental model that reliably replicates human immune responses. Here, a new homozygous humanized human leukocyte antigen (HLA)-A11/DR1 transgenic mouse (HLA-A11(+/+)/DR01(+/+)/H-2-β2m(-/-)/IAβ(-/-)) was generated by crossing HLA-A11 transgenic (Tg) mice with HLA-A2(+/+)/DR01(+/+)/H-2-β2m(-/-)/IAβ(-/-) mice. The HLA-A11-restricted immune response of this mouse model was then examined. HLA-A11 Tg mice expressing a chimeric major histocompatibility complex (MHC) molecule comprising the α1, α2, and β2m domains of human HLA-A11 and the α3 transmembrane and cytoplasmic domains of murine H-2D(b) were generated. The correct integration of HLA-A11 and HLA-DR1 into the genome of the HLA-A11/DR1 Tg mice (which lacked the expression of endogenous H-2-I/II molecules) was then confirmed. Immunizing mice with a recombinant HBV vaccine or a recombinant HIV-1 protein resulted in the generation of IFN-γ-producing cytotoxic T lymphocyte (CTL) and antigen-specific antibodies. The HLA-A11-restricted CTL response was directed at HLA immunodominant epitopes. These mice represent a versatile animal model for studying the immunogenicity of HLA CTL epitopes in the absence of a murine MHC response. The established animal model will also be useful for evaluating and optimizing T cell-based vaccines and for studying differences in antigen processing between mice and humans.