NAT1 (N-Acetyltransferase 1)

Pharmacological NAT10 inhibition (Remodelin treatment) or DKK2 neutralization restored CD8+ T cell function and synergized with anti-PD-1 therapy. Our findings establish the NAT10/DKK2/LRP6/AKT-mTOR/cholesterol axis as a critical regulator of CD8+ T cell dysfunction in CRC, positioning NAT10/DKK2 as a potential target to enhance immunotherapy efficacy.

Notably, combination therapy with an NAT10 inhibitor and anti-PD-L1 antibody demonstrated superior antitumor efficacy compared to monotherapy. In conclusion, NAT10 promotes pancreatic cancer progression and immune evasion by regulating the ETS2-PD-L1 axis and stabilizing KRT8 mRNA, highlighting its potential as a therapeutic target for overcoming immunotherapy resistance.

Our study underscores the multifaceted role of NAT1 in modulating chemo-sensitivity, cellular metabolism, and angiogenesis in CRC. These findings position NAT1 as a compelling candidate for a biomarker and a potential therapeutic target, offering new avenues for CRC management.

Our findings reveal a previously unrecognized ac4C-mediated epigenetic mechanism in PNI and propose a novel therapeutic strategy to improve survival in PDAC patients. NAT10 promotes PNI via ac4C modification in PDAC.

This might explain, in part, why some cancer patients with low NAT1 expression in their tumour tissue show poorer survival outcomes compared to those with high NAT1 expression. The current study demonstrated that NAT1 enzymatic activity is important for metabolism in cancer cell-lines and increasing NAT1 activity may better equip cells to survive under stressed conditions by increasing reserve respiratory capacity.

Additionally, T cells from older individuals with lower NAT10 levels show proliferative defects, which may partially account for impaired antiviral responses in older individuals. This study reveals a mechanism governing T cell expansion, signal-dependent mRNA degradation induction and the potential in vivo biological significance of ac4C modification in T cell-mediated immune responses.

NAT10 regulated glycolysis and apoptosis in NSCLC via ac4C acetylating ENO1, which might provide new ideas for the clinical treatment of NSCLC.

Our study elucidates the mechanism by which the NAT10/DDX5/HMGB1 axis promotes the immunosuppression of NPC by promoting T-cell dysfunction. In addition, NAT10 knockdown can enhance anti-PD-1 treatment sensitivity as a combination therapy for NPC.

Rapidly developed chemoresistance to dacarbazine (DTIC) is a major obstacle in the clinical management of melanoma; however, the roles and mechanisms of epi-transcriptomic RNA modification in this process have not been investigated...Finally, pharmacological inhibition of NAT10 with Remodelin sensitized melanoma cells to DTIC treatment in vitro and in a mouse xenograft model. Our study elucidates the previously unrecognized role of NAT10-mediated ac4C modification in the chemoresistance of melanoma and provides a rationale for developing new strategies to overcome chemoresistance in melanoma patients.

By analyzing the database of miR-1290 target gene NAT1, we verified that miR-1290 could regulate the expression of NAT1. These data provide fresh insights into the biology of breast cancer therapy by demonstrating how the epigenetic factor LSD1 stimulates the breast cancer cells' invasion and migration via controlling exosomal miRNA.

Cells treated with Cmp350 were almost exclusively dependent on glucose as a fuel source. We postulate that Cmp350 is an excellent lead compound for the development of NAT1-targeted inhibitors as both experimental tools and therapeutics in the treatment of hypermetabolic diseases such as amyotrophic lateral sclerosis, cancer cachexia, and sepsis.

We propose that CTSL and C/EBPβp27 may represent a novel therapeutic target for breast cancer treatment. [BMB Reports 2024; 57(6): 293-298].