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: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.
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.
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.