N-acetyltransferase 10 (NAT10) is an important acetyltransferase that regulates telomerase activity and participates in DNA damage reactions, ribosomal RNA (rRNA) transcriptional activation, cell division, microtubule acetylation, and other important cellular processes. Abnormalities in the expression or distribution of NAT10 result in diseases such as Hutchinson-Gilford progeria syndrome (HGPS) and various tumors, with serious consequences. Remodelin, an inhibitor of NAT10, delays HGPS progression; many studies have been conducted on its role in tumor therapy. A major breakthrough in the study of NAT10 was the discovery of mRNA N4-acetylcytidine (ac4C) modification, which can increase mRNA stability and translation efficiency significantly. In addition, NAT10 modifies the mRNA of ac4C, which is associated with tumor development. Here, we present a review of pertinent studies focusing on NAT10, particularly its role in cancer, to provide researchers with a concise and informative summary of the current state of knowledge about this topic. The conclusions drawn from this review could provide a new direction for tumor treatment.

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway.

BACKGROUND: Lung cancer remains the foremost reason of cancer-related mortality, with invasion and metastasis profoundly influencing patient prognosis. N-acetyltransferase 10 (NAT10) catalyzes the exclusive N (4)-acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role in non-small cell lung cancer (NSCLC) invasion and metastasis remains unclear. Our study delves into the clinical significance and functional aspects of NAT10 in NSCLC.
METHODS: We investigated NAT10\'s clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT-PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10\'s effects. A series of assays were carried out, including CCK-8, colony formation, wound healing, and transwell assays, to elucidate NAT10\'s role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient-derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings.
RESULTS: Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E-cadherin level whereas decreased N-cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial-mesenchymal transition (EMT) pathway.
CONCLUSIONS: Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition.

BACKGROUND: Ogden syndrome is an exceptionally rare X-linked disease caused by mutations in the NAA10 gene. Reported cases of this syndrome are approximately 20 children and are associated with facial dysmorphism, growth delay, developmental disorders, congenital heart disease, and arrhythmia.
METHODS: We present the clinical profile of a 3-year-old girl with Ogden syndrome carrying a de novo NAA10 variant [NM_003491:c.247C>T, p.(Arg83Cys)]. During infancy, she exhibited features such as left ventricular hypertrophy, protruding eyeballs, and facial deformities.
METHODS: Clinical diagnosis included Ogden syndrome, congenital heart disease (obstructive hypertrophic cardiomyopathy, left ventricular outflow tract obstruction, mitral valve disease, tricuspid valve regurgitation), tonsillar and adenoidal hypertrophy, and speech and language delay.
METHODS: The girl was considered to have hypertrophic cardiomyopathy (HCM) and received oral metoprolol as a treatment for HCM at our hospital. The drug treatment effect was not ideal, and her hypertrophy myocardial symptoms were aggravated and she had to be hospitalized for surgery.
RESULTS: The girl underwent a modified Morrow procedure under cardiopulmonary bypass and experienced a favorable postoperative recovery. No pulmonary infections or significant complications were observed during this period. The patient\'s family expressed satisfaction with the treatment process.
CONCLUSIONS: The case emphasizes the HCM of Odgen syndrome, and early surgery should be performed if drug treatment is ineffective.

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N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification is crucial for mRNA stability and translation efficiency, yet the underlying function in mammalian preimplantation embryos remains unclear. Here, we characterized the ac4C modification landscape in mouse early embryos and found that the majority of embryos deficient in ac4C writer-NAT10 failed to develop into normal blastocysts. Through single-cell sequencing, RNA-seq, acetylated RNA immunoprecipitation combined with PCR (acRIP-PCR), and embryonic phenotype monitoring, Nop2 was screened as a target gene of Nat10. Mechanistically, Nat10 knockdown decreases the ac4C modification on Nop2 mRNA and reduces RNA and protein abundance by affecting the mRNA stability of Nop2. Then, depletion of NOP2 may inhibit the translation of transcription factor TEAD4, resulting in defective expression of the downstream lineage-specific gene Cdx2, and ultimately preventing blastomeres from undergoing the trophectoderm (TE) fate. However, exogenous Nop2 mRNA partially reverses this abnormal development. In conclusion, our findings demonstrate that defective ac4C modification of Nop2 mRNA hinders the morula-to-blastocyst transition by influencing the first cell fate decision in mice.

Nα-acetyltransferase 10 protein (Naa10p) is known as the catalytic subunit of N-terminal acetyltransferases A (NatA) complex, associating with Naa15p to acetylate N-termini of the human proteome. Recent investigations have unveiled additional functions for Naa10p, encompassing lysine ε-acetylation and acetyltransferase-independent activities. Its pleiotropic roles have been implicated in diverse physiological and pathological contexts. Emerging evidence has implicated Naa10p in cancer progression, demonstrating dual attributes as an oncogene or a tumor suppressor contingent on the cancer type and acetyltransferase activity context. In this comprehensive review, we present a pan-cancer analysis aimed at elucidating the intricacies underlying Naa10p dysregulation in cancer. Our findings propose the potential involvement of c-Myc as a modulatory factor influencing Naa10p expression. Moreover, we provide a consolidated summary of recent advancements in understanding the intricate molecular underpinnings through which Naa10p contributes to cancer cell proliferation and metastasis. Furthermore, we delve into the multifaceted nature of Naa10p\'s roles in regulating cancer behaviors, potentially attributed to its interactions with a repertoire of partner proteins. Through an exhaustive exploration of Naa10p\'s functions, spanning its acetylation activity and acetyltransferase-independent functionalities, this review offers novel insights with implications for targeted therapeutic strategies involving this pivotal protein in the realm of cancer therapeutics.

BACKGROUND: Esophageal squamous carcinoma (ESCC) is a common malignancy that originates in the digestive tract. Lymph node metastasis (LNM) is a complicated process, and tumor lymphangiogenesis has been reported to be associated with the spread of tumor cells to lymph nodes (LNs), including in ESCC. However, little is currently known about the mechanisms involved in lymphangiogenesis in ESCC tumors. According to previous literature, we know that hsa_circ_0026611 expresses at a high level in serum exosomes of patients with ESCC and shows a close association with LNM and poor prognosis. However, details on the functions of circ_0026611 in ESCC remain unclear. We aim to explore the effects of circ_0026611 in ESCC cell-derived exosomes on lymphangiogenesis and its potential molecular mechanism.
METHODS: We firstly examined how circ_0026611 may express in ESCC cells and exosomes by quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). The potential effects circ_0026611 may exert on lymphangiogenesis in ESCC cell-derived exosomes were assessed afterward via mechanism experiments.
RESULTS: circ_0026611 high expression pattern was confirmed in ESCC cells and exosomes. ESCC cell-derived exosomes promoted lymphangiogenesis by transferring circ_0026611. Besides, circ_0026611 interacted with N-α-acetyltransferase 10 (NAA10) to inhibit NAA10-mediated prospero homeobox 1 (PROX1) acetylation with subsequent ubiquitination and degradation. Furthermore, circ_0026611 was verified to promote lymphangiogenesis in a PROX1-mediated manner.
CONCLUSIONS: Exosomal circ_0026611 inhibited PROX1 acetylation and ubiquitination to promote lymphangiogenesis in ESCC.

UNASSIGNED: Bladder cancer (BLCA) is one of the most common urological malignancies globally, posing a severe threat to public health. In combination with protein-protein interaction (PPI) network analysis of proteomics, Gene Set Variation Analysis (GSVA) and \"CancerSubtypes\" package of R software for transcriptomics can help identify biomarkers related to BLCA prognosis. This will have significant implications for prevention and treatment.
UNASSIGNED: BLCA data were downloaded from The Cancer Genome Atlas (TCGA) database and GEO database (GSE13507). GSVA analysis converted the gene expression matrix to the gene set expression matrix. \"CancerSubtypes\" classified patients into three subtypes and established a prognostic model based on differentially expressed gene sets (DEGSs) among the three subtypes. For genes from prognosis-related DEGSs, functional and pathway enrichment analyses and PPI network analysis were carried out. The Human Protein Atlas (HPA) database was used for validation. Finally, the proportion of tumor-infiltrating immune cells (TIICs) was determined using the CIBERSORT algorithm.
UNASSIGNED: In total, 414 tumor samples and 19 adjacent-tumor samples were obtained from TCGA, with 145 samples belonging to subtype A, 126 samples belonging to subtype B, and 136 samples belonging to subtype C. Then, we identified 83 DEGSs and constituted a prognostic signature with two of them: \"GSE1460_CD4_THYMOCYTE_VS_THYMIC_STROMAL_CELL_DN\" and \"MODULE_253.\" Finally, five subnets of two PPI networks were established, and nine core proteins were obtained: CDH2, COL1A1, EIF2S2, PSMA3, NAA10, DNM1L, TUBA4A, KIF11, and KIF23. The HPA database confirmed the expression of the nine core proteins in BLCA tissues. Furthermore, EIF2S2, PSMA3, DNM1L, and TUBA4A could be novel BLCA prognostic biomarkers.
UNASSIGNED: In this study, we discovered two gene sets linked to BLCA prognosis. PPI analysis confirmed the network\'s core proteins, and several newly discovered biomarkers of BLCA prognosis were identified.

N-α-Acetyltransferase 10 (NAA10) was reported to be involved in tumour invasion and metastasis in several of tumours. However, the role and mechanism of NAA10-mediated invasion and metastasis in oral squamous cell carcinoma (OSCC) remains undetermined. Herein, our study showed that NAA10 inhibits cell migration and invasion in vitro and attenuates the xenograft tumorigenesis in nude mice. Mechanistically, we demonstrated that there is a physical interaction between NAA10 and RelA/p65 in OSCC cells, thereby preventing RelA/p65-mediated transcriptional activation of Pirh2. Consequently, inhibition of Pirh2 increased p53 level and suppressed the expression of p53 downstream targets, matrix metalloprotein-2 (MMP-2) and MMP-9. Therefore, NAA10 may function as a tumour metastasis suppressor in the progression of OSCC by targeting Pirh2-p53 axis and might be a prognostic marker as well as a therapeutic target for OSCC.