RESUMO
Ferroptosis is a new form of regulated cell death caused by the iron-dependent peroxidation of phospholipids and is related to cell metabolism, redox homeostasis and various signalling pathways related to cancer. The long non-coding RNA (lncRNA) KB-1460A1.5 acts as a tumour suppressor gene to regulate tumour growth in gliomas, but its molecular network regulatory mechanism is still unclear. In this study, we found that KB-1460A1.5 can induce ferroptosis in glioma and enhance sensitivity to RSL3, a ferroptosis inducer. Tandem mass tag proteomics and nontargeted metabolomics suggest that KB-1460A1.5 affects polyunsaturated fatty acid metabolic processes. Gas chromatography-mass spectrometry-based medium- and long-chain fatty acid-targeted metabolomics confirmed that upregulation of KB-1460A1.5 decreased the levels of monounsaturated fatty acids, oleic acid (OA) and palmitoleic acid (PO) in glioma cells. The addition of OA and PO restored KB-1460A1.5-induced cellular ferroptosis. Molecularly, KB-1460A1.5 inhibited the mammalian target of rapamycin signalling pathway to suppress the expression of downstream sterol regulatory element-binding protein 1 (SREBP-1), thereby attenuating the stearoyl-CoA desaturase-1 (SCD1)-mediated desaturation of polyunsaturated fatty acids. Finally, an animal model of subcutaneous glioma confirmed that KB-1460A1.5 could inhibit tumour progression, SREBP-1/SCD1 expression and ferroptosis. In conclusion, increasing the expression level of KB-1460A1.5 in glioma can promote the induction of oxidative stress and ferroptosis in cancer cells through SREBP-1/SCD1-mediated adipogenesis, demonstrating therapeutic potential in preclinical models.
Assuntos
Ácidos Graxos Insaturados , Ferroptose , Glioma , RNA Longo não Codificante , Estearoil-CoA Dessaturase , Proteína de Ligação a Elemento Regulador de Esterol 1 , Serina-Treonina Quinases TOR , Ferroptose/genética , RNA Longo não Codificante/genética , Glioma/patologia , Glioma/metabolismo , Glioma/genética , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Humanos , Animais , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/farmacologia , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Transdução de Sinais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamento farmacológicoRESUMO
Plants actively recruit microbes from the soil, forming species-specific root microbiomes. However, their relationship with plant adaptations to temperature and precipitation remains unclear. Here we examined the host-selected and conserved microbiomes of 13 native plant species in the Xilingol steppe, Inner Mongolia, a semi-arid region in China. By calculating the global precipitation and temperature niches of these plants, considering plant phylogenetic distances, and analyzing functional traits, we found that these factors significantly influenced the rhizosphere microbiome assembly. We further quantified the strength of host selection and observed that plants with wider precipitation niches exhibited greater host selection strength in their rhizosphere microbiome assembly and higher rhizosphere bacterial diversity. In general, the rhizosphere microbiome showed a stronger link to plant precipitation niches than temperature niches. Haliangium exhibited consistent responsiveness to host characteristics. Our findings offer novel insights into host selection effects and the ecological determinants of wild plant rhizosphere microbiome assembly, with implications for steering root microbiomes of wild plants and understanding plant-microbiome evolution.
RESUMO
The emergence of alternative stable states in forest systems has significant implications for the functioning and structure of the terrestrial biosphere, yet empirical evidence remains scarce. Here, we combine global forest biodiversity observations and simulations to test for alternative stable states in the presence of evergreen and deciduous forest types. We reveal a bimodal distribution of forest leaf types across temperate regions of the Northern Hemisphere that cannot be explained by the environment alone, suggesting signatures of alternative forest states. Moreover, we empirically demonstrate the existence of positive feedbacks in tree growth, recruitment and mortality, with trees having 4-43% higher growth rates, 14-17% higher survival rates and 4-7 times higher recruitment rates when they are surrounded by trees of their own leaf type. Simulations show that the observed positive feedbacks are necessary and sufficient to generate alternative forest states, which also lead to dependency on history (hysteresis) during ecosystem transition from evergreen to deciduous forests and vice versa. We identify hotspots of bistable forest types in evergreen-deciduous ecotones, which are likely driven by soil-related positive feedbacks. These findings are integral to predicting the distribution of forest biomes, and aid to our understanding of biodiversity, carbon turnover, and terrestrial climate feedbacks.