ABSTRACT
Alpha beta hydrolase domain containing 5 (ABHD5) is an essential coactivator of adipose triglyceride lipase (ATGL), a rate-limiting enzyme in various cell types that promotes the hydrolysis of triacylglycerol (TG) into diacylglycerol (DG) and fatty acid (FA). It acts as a critical regulatory factor in cellular lipid metabolism. The reprogramming of lipid metabolism is one of the hallmarks of cancer, suggesting that altering lipid metabolism could become a new strategy for tumor treatment. Research has revealed a close association between ABHD5 and the development and progression of malignancies. This review summarizes the role of ABHD5 in various malignant tumors and explores the different signaling pathways and metabolic routes that may be involved, providing a comprehensive mechanistic understanding of ABHD5.
ABSTRACT
Gene therapy has shown remarkable effectiveness in the management of disease like cancer and inflammation as a revolutionary therapeutic. Nonetheless, therapeutic drug target discovery, efficient gene delivery, and gene delivery vehicles continue to be significant obstacles. Due to their effective gene transport capabilities and low immunogenicity, supramolecular polymers have garnered significant interest. Herein, ABHD5 is identified as a potential therapeutic target since it is dysregulated in hepatocellular carcinoma (HCC). Interestingly, the downregulation of ABHD5 could induce programmed death-ligand 1 (PD-L1) expression in liver cancer, which may contribute to the immunosuppression. To overcome the immunosuppression caused by PD-L1, an injectable hydrogel is designed to achieve efficient abhydrolase domain containing 5 (ABHD5) gene delivery via the host-guest interaction with branched polyethyleneimine-g-poly (ethylene glycol), poly (ethylene oxide) and poly (propylene oxide) block copolymers and α-CD (PPA/CD), demonstrating the capability for sustained gene release. The co-assembly hydrogel demonstrates good biocompatibility and enhanced gene transfection efficiency, efficiently triggering tumor cell apoptosis. Overall, the results of this study suggest that ABHD5 is a potential therapeutic target, and that a host-guest-based supramolecular hydrogel could serve as a promising platform for the inhibition of HCC.
ABSTRACT
Triple-negative breast cancer (TNBC) is a specific type of breast cancer that exhibits poor prognosis and complex tumor heterogeneity. The unique immune tumor microenvironment reveals great potential of immunotherapy in TNBC. Triptolide, a potential regulator of immune-related signaling, has shown potent antitumor activity in TNBC. However, the molecular mechanism of triptolide in TNBC is still controversial. This study identified interferon-γ (IFN-γ) as a therapeutical target of triptolide based on the analysis of prognostic biomarkers in TNBC. IFN-γ is an important component of immunotherapy and contributes to antitumor immune activation. Triptolide was found to significantly reverse the IFN-γ-inducible programmed death-ligand 1 (PD-L1) in TNBC. The combined treatment of triptolide and IFN-γ in a hydrogel delivery system remarkably induced the cytotoxic CD8 + T lymphocytes activation, showing a synergistic effect on the potent tumor inhibition.