RESUMO
The oncogene Aurora kinase A (AURKA) has been implicated in various tumor, yet its role in meningioma remains unexplored. Recent studies have suggested a potential link between AURKA and ferroptosis, although the underlying mechanisms are unclear. This study presented evidence of AURKA upregulation in high grade meningioma and its ability to enhance malignant characteristics. We identified AURKA as a suppressor of erastin-induced ferroptosis in meningioma. Mechanistically, AURKA directly interacted with and phosphorylated kelch-like ECH-associated protein 1 (KEAP1), thereby activating nuclear factor erythroid 2 related factor 2 (NFE2L2/NRF2) and target genes transcription. Additionally, forkhead box protein M1 (FOXM1) facilitated the transcription of AURKA. Suppression of AURKA, in conjunction with erastin, yields significant enhancements in the prognosis of a murine model of meningioma. Our study elucidates an unidentified mechanism by which AURKA governs ferroptosis, and strongly suggests that the combination of AURKA inhibition and ferroptosis-inducing agents could potentially provide therapeutic benefits for meningioma treatment.
Assuntos
Aurora Quinase A , Ferroptose , Proteína Forkhead Box M1 , Meningioma , Fator 2 Relacionado a NF-E2 , Piperazinas , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Aurora Quinase A/metabolismo , Aurora Quinase A/genética , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Animais , Camundongos , Meningioma/metabolismo , Meningioma/genética , Meningioma/patologia , Piperazinas/farmacologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genéticaRESUMO
Abundant hybrid sediments composed of clastic rocks and carbonate rocks were deposited in the Devonian Yangmaba Formation in the northwestern of Sichuan Basin. Based on the measurement of the Ganxi section in detail, combined with the observation of the 30 slices, the hybrid facies, and hybrid sequence, the hybrid deposit mechanism and its controlling factors of the Yangmaba Formation were analyzed. It shows that the hybrid facies consists of the hybrid shore at the lower and clastic hybrid shelf and carbonate hybrid shelf deposits at the middle-upper of the Yangmaba Formation. The hybrid sequence, which can be divided into four sedimentary system tracts: the shelf-margin systems tract (SMST), the transgressive system tract (TST), the early highstand systems tract (EHST), and the late highstand systems tract (LHST), was developed in the Yangmaba Formation. There are three hybrid mechanisms including punctuated mixing, facies mixing, and in situ mixing, and the first two are the main types in the Yangmaba Formation. The punctuated mixing and in situ mixing are the main hybrid mechanisms of hybrid shore and clastic hybrid shelf deposits, and the facies mixing is the main hybrid mechanism of clastic hybrid shelf and carbonate hybrid shelf deposits. The hybrid mechanisms are different among the system tracts: the punctuated mixing is the main mixing manner in the SMST and LHST and the facies mixing developed in the TST and EHST. Storm action is the most important controlling factor of punctuated mixing of the Yangmaba Formation. Relative sea level change, carbonate productivity or the rate of terrestrial clastic supply, and climate change are factors that control and affect hybrid deposits. SMST and HST are mainly related to changes in the relative sea level, while TST is controlled by sedimentary source recharge, and climate change affects the hybrid action of system tracts to varying degrees.
