NAT10 modulates fatty acid metabolism of palmitate driven MCF7 in ac4C dependent manner
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA863318 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20700720_1.fastq.gz | Fastqsanger.gz | |||
| SRR20700720_2.fastq.gz | Fastqsanger.gz | |||
| SRR20700721_1.fastq.gz | Fastqsanger.gz | |||
| SRR20700721_2.fastq.gz | Fastqsanger.gz | |||
| SRR20700722_1.fastq.gz | Fastqsanger.gz |
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Project description:We show that non-toxic exogenous palmitate uptake in MCF7 cells promotes NAT10 expression and NAT10-dependent ac4C RNA modification. It was previously reported that NAT10 modulates the addition of ac4C on RNA transcripts in normal and cancer conditions. However, no study report the impact of NAT10 in palmitate driven cells. Here we performed RNA immunoprecipitation sequencing (RIP-seq) in palmitate loaded MCF7 knockdown with NAT10 siRNA. Based on the pathways and enrichment landscape identified. We found that ac4C peaks of fatty acid metabolic genes including ELOVL6, ACSL1, ACSL3, ACSL4, ACADSB and ACAT1 were significantly decreased upon knockdown with NAT10 siRNA. Overall, our results revealed the impact of NAT10 as a regulator of fatty acid metabolism in ac4C-dependent manner
2022-08-03 | GSE210017 | GEO
Project description:RNA modification play vital roles in renal fibrosis. However, whether ac4C modification functions in renal fibrogenesis remains unknown. Here, we found that NAT10-ac4C axis plays pro—fibrotic role in kidney. ac4C RIP sequencing demonstrated NAT10-ac4C axis functions via regulating multiple master genes of exosome secretion in tubular epithelial cells. In summary, targeting NAT10-ac4C axis is a promising strategy for renal fibrosis.
2024-11-30 | GSE248203 | GEO
Project description:Hepatocellular carcinoma (HCC) is characterized by high morbidity and mortality, withlimited effective treatment options. NAT10 is the only known acetyltransferase formRNA ac4C modification and is recognized as a biomarker for HCC, promoting itsprogression. However, the critical role of NAT10 in hepatocarcinogenesis remains tobe fully elucidated, and the identification of suitable small-molecule inhibitors targetingNAT10 is of great interest. Here, we report that NAT10 promotes HCC progression bystabilizing SMAD3 mRNA through ac4C modification. Clinically, NAT10 is highlyexpressed in HCC tissues and is significantly associated with poor prognosis.Functionally, NAT10 downregulation inhibits HCC cell proliferation, invasion, andepithelial-mesenchymal transition (EMT), while promoting anoikis in vitro.Additionally, NAT10 depletion significantly impairs tumor growth, metastasis, andhepatocarcinogenesis in vivo. Mechanistically, NAT10 enhances oncogene SMAD3mRNA stability via ac4C modification, thereby activating TGF-β signaling pathway.We also identify a novel small-molecule inhibitor, NAT10-2023, which effectivelyblocks NAT10 activity. Notably, NAT10-2023 treatment significantly reducesintracellular RNA ac4C modification levels and disrupts NAT10-RNA interactions,leading to suppressed tumor progression. Overall, NAT10 drives HCC progression viaSMAD3 mRNA stability regulation and NAT10-2023 could be a promising therapeuticcandidate for targeting NAT10 in cancer treatment.
2026-05-18 | GSE297856 | GEO
Project description:Hepatocellular carcinoma (HCC) is characterized by high morbidity and mortality, withlimited effective treatment options. NAT10 is the only known acetyltransferase formRNA ac4C modification and is recognized as a biomarker for HCC, promoting itsprogression. However, the critical role of NAT10 in hepatocarcinogenesis remains tobe fully elucidated, and the identification of suitable small-molecule inhibitors targetingNAT10 is of great interest. Here, we report that NAT10 promotes HCC progression bystabilizing SMAD3 mRNA through ac4C modification. Clinically, NAT10 is highlyexpressed in HCC tissues and is significantly associated with poor prognosis.Functionally, NAT10 downregulation inhibits HCC cell proliferation, invasion, andepithelial-mesenchymal transition (EMT), while promoting anoikis in vitro.Additionally, NAT10 depletion significantly impairs tumor growth, metastasis, andhepatocarcinogenesis in vivo. Mechanistically, NAT10 enhances oncogene SMAD3mRNA stability via ac4C modification, thereby activating TGF-β signaling pathway.We also identify a novel small-molecule inhibitor, NAT10-2023, which effectivelyblocks NAT10 activity. Notably, NAT10-2023 treatment significantly reducesintracellular RNA ac4C modification levels and disrupts NAT10-RNA interactions,leading to suppressed tumor progression. Overall, NAT10 drives HCC progression viaSMAD3 mRNA stability regulation and NAT10-2023 could be a promising therapeuticcandidate for targeting NAT10 in cancer treatment.
2026-05-18 | GSE297009 | GEO
Project description:R-loop remodeling dynamically regulates chromatin states and gene expression; however, its exploitation by cancer to sustain self-renewal and malignancy remains poorly understood. Here, we found that glioblastoma (GBM) stem cells (GSCs) display highly active R-loops compared to differentiated tumor progeny and neural stem cells (NSCs). Genome-wide mapping by R-loop RNA chromatin immunoprecipitation sequencing (RR-ChIP-seq) revealed cell-specific enrichment and spatial accumulation of R-loops at promoter-proximal regions in GSCs, correlating with active transcription and open chromatin states. We profiled R-loop interactomes and identified N-Acetyltransferase 10 (NAT10), an RNA N4-acetylcytidine (ac4C)-modifying enzyme, as a high-affinity R-loop-binding protein in GSCs. Driven by transcriptional activation via OLIG1, NAT10 was overexpressed in GSCs. ac4C-specific RNA immunoprecipitation sequencing (ac4C-RIP-seq) on R-loop RNA revealed genome-wide mapping of ac4C-modified R-loops with abundant ac4C-modified R-loops that regulated the genome. NAT10 catalyzed widespread ac4C deposition on the RNA stand of R-loops, stabilizing promoter-associated R-loops, and facilitating open chromatin to sustain self-renewal through core stemness regulators, including transcription factor EGR1. NAT10 knockdown suppressed proliferation and maintenance in vitro and attenuated tumor growth in vivo. Pharmacological inhibition of NAT10/ac4C-modified R-loops using the small-molecule inhibitor remodelin phenocopied NAT10 genetic targeting, demonstrating therapeutic promise for targeting cancer.
2026-04-10 | PXD077002 | Pride
Project description:Pancreatic cancer is a lethal diease with high tendency of metastasis. Howerver, the mechanisms of pancreatic cancer are sitill unclear. To explore the roles of N4-acetylation (ac4C) RNA modification and its involved N-Acetyltransferase 10 (NAT10) in pancreatic ductal adenocarcinoma (PDAC), we performed profiling by high throughput sequencing. In this study, we investigate the effects of NAT10 knockdown on N4-acetylcytidine (ac4C) modification in mRNA within PANC-1 cells using ac4C-seq. By employing RNA interference to specifically knock down NAT10 expression in PANC-1 cells, we aim to elucidate its impact on ac4C RNA modifications, which have been implicated in various cellular processes and cancer progression. Total RNA was extracted and mRNA was captured and treated with sodium borohydride (NaBH4) for detection of ac4C sites.Following library preparation, sequencing was performed on an Illumina Novaseq 6000 platform. Bioinformatics analyses identified significant changes in ac4C modification patterns due to NAT10 depletion. This dataset provides a valuable resource for further exploration of ac4C modifications in mRNA and their role in PDAC.
2025-03-26 | GSE275963 | GEO
Project description:N4-acetylcytidine (ac4C), a conserved chemical modification in eukaryotic prokaryotes that is catalyzed by the N-acetyltransferase 10 (NAT10) enzyme, plays a crucial role in promoting mRNA stability and translation. However, the biological function and mechanisms of NAT10-mediated ac4C in human cancer were poorly defined. In order to investigate the regulatory mechanism of NAT10 in gastric cancer, we performed ac4C RIP-seq(acRIP-seq) analysis in AGS cells with NAT10 knockout compared with control in two repeats.
2024-07-07 | GSE180494 | GEO
Project description:In our study, we aimed to identify the pathways and genes closely related to DVT. Through proteomic analysis, we found that the ferroptosis signaling pathway showed differential expression, and we also discovered that NAT10 (a key acetyltransferase modified by ac4C) was significantly overexpressed in DVT mice. Based on this discovery, we further investigated the downstream genes regulated by NAT10. We found that NAT10 enhances the stability of HMOX1 through ac4C modification, which results in iron overload and lipid peroxides, thereby forming a positive feedback loop that exacerbates DVT.
2026-01-26 | PXD067933 | Pride
Project description:RNA modification represents an important post-transcriptional regulatory mechanism in acute myeloid leukemia (AML), however the function and mechanism of RNA acetylation ac4C in AML remains elusive. Here, we report that NAT10, as the ac4C writing enzyme, plays a critical oncogenic function in AML and represents a promising therapeutic target for AML. To understand the mechanisms underlying the function of NAT10 as an RNA ac4C writer in AML, we profiled ac4C modification in the transcriptome of MOLM13 cells using a refined ac4C RNA immunoprecipitation and high throughput sequencing (RacRIP-seq) protocol, and performed systematic calibration with a modification-free control library generated from the in vitro- transcribed MOLM13 transcriptome (referred to as IVT control) to eliminate most of the false- positive signals. We also applied the RacRIP-seq in NAT10 knockdown and control MOLM13 cells to characterize NAT10 targets.
2024-08-26 | GSE246505 | GEO
Project description:Background: Heart failure (HF), characterized by cardiac remodeling, is associated with abnormal epigenetic processes and aberrant gene expression. Here, we aimed to elucidate the effects and mechanisms of N-acetyltransferase 10 (NAT10)-mediated N4?acetylcytidine (ac4C) acetylation during cardiac remodeling. Methods: NAT10 and ac4C expression were detected in both human and mouse subjects with cardiac remodeling through multiple assays. Subsequently, acetylated RNA immunoprecipitation and sequencing (acRIP-seq), thiol (SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq), and ribosome sequencing (Ribo-seq) were employed to elucidate the role of ac4C-modified post-transcriptional regulation in cardiac remodeling. Additionally, functional experiments involving the overexpression or knockdown of NAT10 were conducted in mice models challenged with Ang II and transverse aortic constriction (TAC). Results: NAT10 expression and RNA ac4C levels were increased in in vitro and in vivo cardiac remodeling models, as well as in patients with cardiac hypertrophy. Silencing and inhibiting NAT10 attenuated Ang II-induced cardiomyocyte hypertrophy and cardio-fibroblast activation. Next-generation sequencing revealed ac4C changes in both mice and humans with cardiac hypertrophy were associated with changes in global mRNA abundance, stability and translation efficiency. Mechanistically, NAT10 could enhance the stability and translation efficiency of CD47 and ROCK2 transcripts by upregulating their mRNA ac4C modification, thereby resulting in an increase in their protein expression during cardiac remodeling. Furthermore, the administration of Remodelin, a NAT10 inhibitor, has been shown to prevent cardiac functional impairments in mice subjected to TAC by suppressing cardiac fibrosis, hypertrophy, and inflammatory responses, while also regulating the expression levels of CD47 and ROCK2. Conclusions: Therefore, our data suggest that modulating epitranscriptomic processes, such as ac4C acetylation through NAT10, may be a promising therapeutic target against cardiac remodeling.
2023-10-31 | GSE233736 | GEO