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Function and Mechanism of NAT10-mediated N4-acetylcytidine modification in osteosarcoma [mRNA-seq]

GSE237541 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2024/08/09 Platform GPL23227
Summary
Despite the advance in diagnosis and treatment, the prognosis of osteosarcoma patients remains unsatisfied. Therefore, it is imperative to identify novel therapeutic targets for osteosarcoma. Through RNA sequencing (RNA-seq) combined with functional screening, N4-acetylcytidine (ac4C) acetyltransferase 10 (NAT10) was identified as a candidate therapeutic target in osteosarcoma. Upregulated NAT10 correlated with poor prognosis in osteosarcoma patients and NAT10 knockout drastically inhibited cell proliferation and metastasis in vitro and in vivo. NAT10 enhanced mRNA stability and translation efficiency of activating transcription factor 4 (ATF4) through ac4C modification. ATF4 induced transcription of asparagine synthetase (ASNS), which catalyzes asparagine (Asn) biosynthesis. Asn promote protein and nucleotide synthesis, facilitating osteosarcoma progression. Overexpression of ATF4, ASNS or supplementation of asparagine rescue the tumor inhibitory effect of NAT10 knockout.
Published in
Targeting NAT10 inhibits osteosarcoma progression via ATF4/ASNS-mediated asparagine biosynthesis
Zou Y, Guo S, Wen L et al. · Cell reports. Medicine 2024 · PMID 39293390 · doi:10.1016/j.xcrm.2024.101728
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Also filed as BioProject PRJNA995608 and SRA study SRP449968. Searching any of these in the dataset finder brings you back here.

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