Acetyl-CoA synthetase 2 (ACSS2), an important member of the acetyl-CoA synthetase (ACSS) family, can catalyze the conversion of acetate to acetyl coenzyme A (acetyl-CoA). Currently, acetyl-CoA is considered an important intermediate metabolite in the metabolism of energy substrates. In addition, nutrients converge through acetyl-CoA into a common metabolic pathway, the tricarboxylic acid cycle and oxidative phosphorylation. Not only does ACSS2 play a crucial role in material energy metabolism, it is also involved in the regulation of various acetylation processes, such as regulation of histone and transcription factor acetylation. ACSS2-mediated regulation of acetylation is related to substance metabolism and tumorigenesis. In mammalian cells, ACSS2 utilizes intracellular acetate to synthesize acetyl-CoA, a step in the process of DNA and histone acetylation. In addition, studies in tumors have shown that cancer cells adapt to the growth conditions in the tumor microenvironment (TME) by activating or increasing the expression level of ACSS2 under metabolic stress. Therefore, this review mainly outlines the role of ACSS2 in substance metabolism and tumors and provides insights useful for investigating ACSS2 as a therapeutic target.

Ferroptosis is a distinct form of cell death characterized by unique morphology, biochemistry, and genetics, playing a crucial role in the initiation, progression, prognosis, and therapeutic strategies of tumors. However, the impact of ferroptosis-related genes (FRGs) on the tumor microenvironment (TME) remains unclear. This study may advance the existing knowledge of FRGs in gastric cancer, and push ahead with more effective prognostic assessment and the development of more effective immunotherapy approaches. FRGs were acquired from the FerrDb database and a consensus clustering technique was adopted to categorize patients with GC into groups in line with the expression profiles of 44 FRGs in order to further investigate the expression properties of these proteins. Assessment of the immune status, microsatellite instability (MSI) and cancer stem cell (CSC) index between the high- and low- risk groups to assess the proportion of TIICs in the TME, ssGSVA was adopted to detect the abundance of infiltrating immune cells from the low-risk and high-risk groups. Expression levels of eight ferroptosis-related genes of prognostic signature in GC tissues and adjacent normal tissues was detected by RT-PCR. In the GC cohort, TP53 has the highest mutation frequency (44 %), and was shown to be highly linked with the expression levels of 11 FRGs. In accordance with the Kaplan-Meier curve, the overall survival time of patients with subtype A (Low FRG-score) discernibly exceeded that of patients with subtype B (High FRG-score).In addition, there is a significant difference in the infiltration of most immune cells between subtype A and subtype B, and some important immune checkpoints (CTLA4, PDCD1, CD274, LAG3, PDCD1LG2, and HAVCR2) have higher expression in cluster A. Finally, low FRG-scores were significantly associated with MSI-H status, while high FRG-scores were significantly associated with microsatellite stable status (MSS). FRG-score is negatively related to the cancer stem cell (CSC). Low FRG-score, due to its high microsatellite instability (MSI-H), high mutational load and immune activation, indicates the possible advantage of OS. In addition, the FRG-score was closely related to the cancer stem cell (CSC) index and the sensitive degree of chemotherapeutic drug.

NAT10 (N-acetyltransferase 10) is a nucleolar acetyltransferase with catalytic acetylation function, which is currently the only known acetyltransferase that catalyzes the N4-acetylcytidine (ac4C) modification in RNA. As the “writer” protein for ac4C, NAT10 plays a critical role in various biological and pathological processes. In this article, we first introduce the structural and functional characteristics of NAT10, followed by a comprehensive synthesis of its multifaceted molecular mechanisms orchestrating tumor radiotherapy and chemotherapy resistance. Specifically, we emphasize its roles in hyperactivating DNA damage repair (DDR), driving metabolic reprogramming (including evasion of ferroptosis), and facilitating tumor immune evasion via PD-L1 regulation and T-cell suppression. Furthermore, we critically evaluate the translational implications of NAT10-targeted interventions, highlighting the therapeutic promise of specific inhibitors like Remodelin and the repurposed FDA-approved drug Fludarabine. We believe that understanding the functions and mechanisms of NAT10 in tumors will significantly improve the diagnosis, treatment, and prognosis of cancer.

Esophageal cancer (ESCA) is defined by high incidence and mortality rates. Emerging evidence implicates angiopoietin‑2 (ANGPT2) as a key mediator in human carcinogenesis; however, its precise functional role and underlying mechanisms in ESCA remain incompletely elucidated. Clinical samples and The Cancer Genome Atlas, genotype‑tissue expression and Gene Expression Omnibus databases were first used to analyze ANGPT2 expression, clinical relevance and prognostic value, demonstrating it as an independent prognostic factor and potential oncogene in ESCA. In addition, abnormal ANGPT2 expression affected ESCA migration and invasion in vitro. Subsequently, through correlation, expression and prognostic analyses, the upstream long‑chain non‑coding RNAs and microRNAs that regulate ANGPT2 were identified. In conclusion, gene set enrichment analysis revealed a connection between ANGPT2 and the immune system, with ANGPT2 level showing a strong positive correlation with tumor microenvironment cell infiltration, immune cell markers, and immune checkpoint expression. Furthermore, ANGPT2 expression was significantly associated with sensitivity to chemotherapeutic drugs. To summarize, overexpression of ANGPT2 in ESCA is associated with an unfavorable prognosis and compromised tumor immunity.

Ferroptosis constitutes a novel type of cell death in morphology, biochemistry and genetics, and is tightly associated with the occurrence, development, prognosis and treatment of tumors. Nevertheless, the potential contribution of ferroptosis-related genes (FRGs) to the tumor microenvironment (TME) is indistinct. We delineated and evaluated the expression pattern of FRGs in gastric cancer (GC) samples from the perspectives of genetics and transcription. Subsequently, we discerned two different molecular subtypes and figured out that the changes in multilayer FRGs are linked with the clinicopathological characteristics, prognosis and TME cell infiltration characteristics of patients. Then, we constructed an FRG-score with a view to predicting overall survival (OS) and verified its predictive ability in GC patients. Therefore, we constructed a high-precision nomogram to improve the clinical applicability of the FRG-score. Low FRG-score, due to its high microsatellite instability (MSI-H), high mutational load and immune activation, indicates the possible advantage of OS. In addition, the FRG-score was closely related to the cancer stem cell (CSC) index and the sensitive degree of chemotherapeutic drug. Our generalized study of FRGs in gastric cancer shows their potentialities in the TME, clinicopathological characteristics and prognosis. These results may advance the existing knowledge of FRGs in gastric cancer, and push ahead with more effective prognostic assessment and the development of more effective immunotherapy approaches.