脂质代谢重编程是癌细胞的公认标志。识别食管鳞状细胞癌（ESCC）代谢重编程的潜在调节因子，可以发现潜在的治疗靶点，以改善治疗效果。在这里，我们证明了预mRNA加工因子19（PRP19）在ESCC中介导脂质代谢重编程。PRP19在多个ESCC队列中的表达显著上调，并与不良临床预后相关。PRP19促进了ESCC体内和体外的增殖。通过脂质合成的主要转录因子甾体类固醇调节元件结合蛋白1（SREBF1），PRP19增强了脂肪酸合成。此外，PRP19以N6-甲基腺嘌呤依赖的方式增强了SREBF1 mRNA的稳定性。总的来说，这项研究表明PRP19介导的脂肪酸代谢对ESCC的进展至关重要。定位PRP19是逆转ESCC患者代谢重编程的潜在治疗方法。通过重编程SREBF1依赖的脂肪酸代谢，上调预mRNA加工因子19（PRP19）有助于食管鳞状细胞癌的进展，识别PRP19作为潜在的预后生物标记物和治疗靶点。 © 2023年美国癌症研究协会。

Lipid metabolism reprogramming is a recognized hallmark of cancer cells. Identification of the underlying regulators of metabolic reprogramming in esophageal squamous cell carcinoma (ESCC) could uncover potential therapeutic targets to improve treatment. Here, we demonstrated that pre-mRNA processing factor 19 (PRP19) mediates reprogramming of lipid metabolism in ESCC. Expression of PRP19 was significantly upregulated in multiple ESCC cohorts and was correlated with poor clinical prognosis. PRP19 promoted ESCC proliferation in vitro and in vivo. Upregulation of PRP19 enhanced fatty acid synthesis through sterol regulatory element-binding protein 1 (SREBF1), a major transcription factor of lipid synthase. Moreover, PRP19 enhanced the stability of SREBF1 mRNA in an N6-methyladenosine-dependent manner. Overall, this study shows that PRP19-mediated fatty acid metabolism is crucial for ESCC progression. Targeting PRP19 is a potential therapeutic approach to reverse metabolic reprogramming in patients with ESCC.Upregulation of pre-mRNA processing factor 19 (PRP19) contributes to esophageal squamous cell carcinoma progression by reprogramming SREBF1-dependent fatty acid metabolism, identifying PRP19 as a potential prognostic biomarker and therapeutic target.©2023 American Association for Cancer Research.