GTPase-activating protein-binding protein 2 (G3BP2) is a key stress granule-associated RNA-binding protein responsible for the formation of stress granules (SGs). Hyperactivation of G3BP2 is associated with various pathological conditions, especially cancers. Emerging evidence indicates that post-translational modifications (PTMs) play critical roles in gene transcription, integrate metabolism and immune surveillance. However, how PTMs directly regulate G3BP2 activity is lacking. Here, our analyses identify a novel mechanism that PRMT5-mediated G3BP2-R468me2 enhances the binding to deubiquitinase USP7, which ensures the deubiquitination and stabilization of G3BP2. Mechanistically, USP7- and PRMT5-dependent G3BP2 stabilization consequently guarantee robust ACLY activation, which thereby stimulating de novo lipogenesis and tumorigenesis. More importantly, USP7-induced G3BP2 deubiquitination is attenuated by PRMT5 depletion or inhibition. PRMT5-activity dependent methylation of G3BP2 is required for its deubiquitination and stabilization by USP7. Consistently, G3BP2, PRMT5 and G3BP2 R468me2 protein levels were found positively correlated in clinical patients and associated with poor prognosis. Altogether, these data suggest that PRMT5-USP7-G3BP2 regulatory axis serves as a lipid metabolism reprogramming mechanism in tumorigenesis, and unveil a promising therapeutic target in the metabolic treatment of head and neck squamous carcinoma.

Raw naringenin directly isolated from plants is significantly limited by its poor dissolution rate and low bioavailability for clinical and in vivo studies. This study reported a method for the preparation of naringenin ultrafine powder (NUP) using a novel anti-solvent recrystallization process; preliminary experiments were conducted using six single-factor experiments. The response surface Box–Behnken (BBD) design was used to optimize the level of factors. The optimal preparation conditions of the DMP were obtained as follows: the feed rate was 40.82 mL/min, the solution concentration was 20.63 mg/mL, and the surfactant ratio was 0.62%. The minimum average particle size was 305.58 ± 0.37 nm in the derived optimum conditions. A scanning electron microscope was used to compare and analyze the appearance and morphology of the powder before and after preparation. The characterization results of FTIR, TG and XRD showed that no chemical change occurred in the powder before and after preparation. Through the simulated gastrointestinal juice digestion experiment, it was confirmed that the absorption rate of NUP was 2.96 times and 4.05 times higher than raw naringenin, respectively. Therefore, the results showed that the reduction in the particle size through the use of low-speed recrystallization could improve the absorption rate and provided a feasible approach for the further applications.