ACLY (ATP Citrate Lyase)

Finally, data from the Cancer Genome Atlas showed significantly diminished survival outcomes among ACC patients exhibiting high ACLY or FASN expression. These findings underscore the potential importance of exploring the inhibition of lipid synthesis as a promising avenue for further research in the context of human ACC.

This study reveals a previously unrecognized role of PSMD14-derived lactate in mediating histone lactylation-coupled lipid deposition and tumor progression. Therapeutic co-targeting of PSMD14 and glycolytic lactylation significantly suppresses tumor growth in patient-derived xenograft models, suggesting a promising combinatorial strategy for pancreatic cancer treatment.

This study identified the potential of using metabolic enzymes as biomarkers in identification of lung adenocarcinoma patients. The observations highlighted the significance of lipogenic enzymes mainly ACLY and fatty acid synthase as diagnostic markers in lung adenocarcinoma liquid biopsies.

Downregulation in KICH, on the other hand, agrees with evidence of metabolic stability in certain cancers. These findings might be used in the direction of metabolism-based therapeutic approaches and risk stratification in oncology.

Additionally, FOXO4 suppressed lipid metabolism and cell proliferation in glioma cells by binding to the promoter regions of target genes ACLY and FASN and inhibiting transcription. Furthermore, SRSF10 stabilized SNORD46, which enhanced the SRSF10/SNORD46/FTSJ3/FOXO4 signaling pathway's role as a crucial regulator of glioma cell proliferation and lipid metabolism, presenting potential therapeutic targets for glioma treatment.

Interestingly, our analyses also revealed a reciprocal relationship whereby ACLY itself is a direct transcriptional target of MYC, thus establishing a feedforward loop that is important for leukemia progression. Overall, our results identified a relevant ACLY-MYC axis and unveiled ACLY as a novel promising target for T-ALL treatment.

Follow-up and validation analyses support the robustness of these results. This study illuminates the therapeutic potential of ACLY inhibition in melanoma, with PARP1 implicated as a potential mediator, offering avenues for targeted interventions.

The restoration of c-Myc or ACLY expression attenuated the inhibitory effects of RNF112 on BLCA cell growth, migration, and lipid synthesis. In conclusion, this study confirmed that RNF112 suppressed the proliferation, migration, and lipid synthesis of BLCA cells by facilitating the ubiquitin-mediated degradation of c-Myc.

The mean particle size of potassium hydroxycitrate-loaded exosomes (Exo-KH) and paclitaxel exosomes (Exo-Pac) was 183 nm and 174 nm; they had spherical morphology and encapsulation efficiency of 16.87 ± 2.78% and 27.65 ± 3.23%, respectively...Moreover, the pharmacokinetic study revealed the sustained release of hydroxycitrate (half-life 22.74 h and clearance 0.13 µg/ml) from the exoformulation. Altogether, the study findings highlight the beneficial role of EXO-KH formulation against lung cancer.

In conclusion, our study revealed that M-I inhibits glycolysis, lipid metabolism, induces autophagy in HNC cells and reduces tumor volume in mice. Therefore, M-I-mediated metabolic reprogramming of HNC has the potential for important therapeutic implications.

Nuclear ACSS2 overexpression or ACLY inhibition prevented TEX differentiation and enhanced tumor-specific T cell responses. These findings unveiled a nutrient-instructed histone code governing CD8+ T cell differentiation, with implications for metabolic- and epigenetic-based T cell therapies.

Downregulation of ACLY inhibited GC cell growth in vitro and in vivo. ACSS2 was compensated to increase to maintain cell growth in ACLY-depleted GC cells.