Project description:Fibroblast-like synoviocytes (FLS) exhibit aggressive phenotype, proliferation and decreased cell-contact inhibition,and play a critical role in pathogenesis of rheumatoid arthritis (RA). However, the mechanism underlying these phenotype remains unknown. In this study, we explore the function of ac4c modification in modulating RA FLS aggressive behavior, and reveal the underlying molecular mechanism.
Project description:Fibroblast-like synoviocytes (FLS) exhibit aggressive phenotype, proliferation and decreased cell-contact inhibition,and play a critical role in pathogenesis of rheumatoid arthritis (RA). However, the mechanism underlying these phenotype remains unknown. In this study, we explore the function of ac4c modification in modulating RA FLS aggressive behavior, and reveal the underlying molecular mechanism.
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.
Project description:We performedacRIP-seq between control CRC cells and CRC cells with NAT10 knockdown to identify NAT10 mediates mRNA ac4C modification
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.
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.
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.
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.