下调和上调
β氧化
化学
癌变
卵巢癌
脂质代谢
脂肪酸代谢
癌症研究
脂肪酸合成
泛素连接酶
癌症
脂肪酸
生物化学
生物
泛素
内科学
医学
基因
作者
Shuhua Zhao,Qingqiang Wang,Xiaohong Zhang,Bing Ma,Yuan Shi,Yadong Yin,Wei Yang Kong,Wei Zhang,Jibin Li,Hong Yang
标识
DOI:10.1016/j.freeradbiomed.2024.01.004
摘要
Lipid metabolic reprogramming has been recognized as a hallmark of human cancer. Acetyl-CoA Carboxylases (ACCs) are key rate-limiting enzymes involved in fatty acid metabolism regulation by catalyzing the carboxylation of acetyl-CoA to malonyl-CoA. Previously, most studies focused on the role of ACC1 in fatty acid metabolism in cancer, while the function of ACC2 remains largely uncharacterized in human cancers, especially in ovarian cancer (OC). Here, we show that ACC2 was significantly downregulated in cancerous tissue of OC, and the downregulation of ACC2 is closely associated with lager tumor size, metastases and worse prognosis in OC patients. Downregulation of ACC2 promoted proliferation and metastasis of OC both in vitro and in vivo by enhancing FAO. Notably, mitochondria-associated ubiquitin ligase (MARCH5) was identified to interact with and downregulate ACC2 by ubiquitination and degradation in OC. Moreover, ACC2 downregulation-enhanced FAO contributed to the progression of OC promoted by MARCH5. In conclusion, our findings demonstrate that MARCH5-mediated downregulation of ACC2 promotes FAO and tumorigenesis in OC, suggesting MARCH5-ACC2 axis as a potent candidate for the treatment and prevention of OC.
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