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Abstract：
Renal cell carcinoma (RCC) stands as a prevalent malignancy within urological pathology, exhibiting a noteworthy escalation in its incidence. Despite being a mitochondrial enzyme, the precise role of Acetyl-CoA Acetyltransferase 1 (ACAT1) in RCC remains elusive. In this investigation, we employed bioinformatics methodologies to assess the expression patterns and prognostic significance across various RCC subtypes, encompassing clear cell renal cell carcinoma (ccRCC), papillary cell carcinoma, and chromophobe cell carcinoma. Our findings unveil a close correlation between ACAT1 expression and the prognostic implications specifically within ccRCC. Through both in vitro and in vivo overexpression studies, we delineated the functional and mechanistic facets of ACAT1 in impeding the progression of ccRCC. Our results unequivocally demonstrated that ACAT1 overexpression markedly curtailed proliferation, invasion, and metastasis of ccRCC cells in both in vivo models and cell cultures. Mechanistically, ACAT1\'s inhibitory effect on the AMPK signaling pathway orchestrated a regulatory role in modulating fatty acid metabolism, thereby effectively restraining the advancement of ccRCC. Collectively, our findings underscore ACAT1 as a pivotal tumor suppressor, instrumental in curtailing the proliferation, migration, and invasion of ccRCC by governing fatty acid metabolism through the AMPK signaling pathway. These insights posit ACAT1 as a potential predictive biomarker and therapeutic target warranting further exploration in RCC management.
摘要：
肾细胞癌（RCC）是泌尿外科病理学中普遍存在的恶性肿瘤，表现出值得注意的发病率升级。尽管是线粒体酶，乙酰辅酶A乙酰转移酶1（ACAT1）在RCC中的确切作用仍然难以捉摸。在这次调查中,我们使用生物信息学方法来评估各种RCC亚型的表达模式和预后意义。包括透明细胞肾细胞癌（ccRCC），乳头状细胞癌,和嫌色细胞癌。我们的发现揭示了ACAT1表达与ccRCC中特定的预后意义之间的密切关系。通过体外和体内过表达研究，我们描述了ACAT1阻碍ccRCC进展的功能和机制方面。我们的结果明确表明，ACAT1过表达显著抑制了细胞增殖，入侵,和ccRCC细胞在体内模型和细胞培养物中的转移。机械上,ACAT1对AMPK信号通路的抑制作用协调了调节脂肪酸代谢的调节作用，从而有效地抑制了ccRCC的发展。总的来说，我们的发现强调ACAT1是一个关键的肿瘤抑制因子，有助于遏制扩散，迁移,通过AMPK信号通路控制脂肪酸代谢和ccRCC的侵袭。这些见解认为ACAT1是潜在的预测生物标志物和治疗靶标，值得在RCC管理中进一步探索。
