脂肪酸代谢和脂肪酸新生失调是多种癌症类型的关键驱动因素，通过高度不饱和脂肪酸（HUFA）信号前体（如花生四烯酸）发挥作用。人类11号染色体长臂13区（11q13位点）长期以来被确认为多种人类癌症中最常见的放大区域。负责HUFA生物合成的脂肪酸脱饱和酶基因（FADS1、FADS2和FADS3）定位于11q12-13.1区域。FADS2活性是广泛的，可以通过Δ6、Δ8和Δ4脱饱和反应催化多种不饱和脂肪酸的合成。我们的主要目标是回顾已知和可能的FADS2失调后果，因为其对11q13位点的影响可能驱动各种癌症类型。FADS2沉默可导致MCF7细胞和乳腺癌中5Z,11Z,14Z-20:3硬脂酸的合成。结构上，5Z,11Z,14Z-20:3硬脂酸与花生四烯酸（5Z,8Z,11Z,14Z-20:4）完全相同，只是缺少合成前列腺素、白三烯等花生四烯酸类的内部Δ8双键。棕榈酸对SCD和FADS2都具有底物特异性。对SCD抑制不敏感的黑色素瘤、前列腺癌、肝癌和肺癌细胞显示FADS2活性增加和硬脂酸生物合成增加。在肝细胞癌患者中发现升高的血清粘酸水平表明花生四烯酸需求未得到满足。FADS2循环RNA在结直肠癌和肺癌组织中水平较高。FADS2循环RNA与结直肠癌患者的总体生存时间较短有关。迄今为止的证据支持在未来研究中探索FADS2在一系列肿瘤性疾病中的肿瘤抑制作用。版权所有©2023。由Elsevier Ltd出版。

Dysregulation of fatty acid metabolism and de novo lipogenesis is a key driver of several cancer types through highly unsaturated fatty acid (HUFA) signaling precursors such as arachidonic acid. The human chromosome 11q13 locus has long been established as the most frequently amplified in a variety of human cancers. The fatty acid desaturase genes (FADS1, FADS2 and FADS3) responsible for HUFA biosynthesis localize to the 11q12-13.1 region. FADS2 activity is promiscuous, catalyzing biosynthesis of several unsaturated fatty acids by Δ6, Δ8, and Δ4 desaturation. Our main aim here is to review known and putative consequences of FADS2 dysregulation due to effects on the 11q13 locus potentially driving various cancer types. FADS2 silencing causes synthesis of sciadonic acid (5Z,11Z,14Z-20:3) in MCF7 cells and breast cancer in vivo. 5Z,11Z,14Z-20:3 is structurally identical to arachidonic acid (5Z,8Z,11Z,14Z-20:4) except it lacks the internal Δ8 double bond required for prostaglandin and leukotriene synthesis, among other eicosanoids. Palmitic acid has substrate specificity for both SCD and FADS2. Melanoma, prostate, liver and lung cancer cells insensitive to SCD inhibition show increased FADS2 activity and sapienic acid biosynthesis. Elevated serum mead acid levels found in hepatocellular carcinoma patients suggest an unsatisfied demand for arachidonic acid. FADS2 circular RNAs are at high levels in colorectal and lung cancer tissues. FADS2 circular RNAs are associated with shorter overall survival in colorectal cancer patients. The evidence thusfar supports an effort for future research on the role of FADS2 as a tumor suppressor in a range of neoplastic disorders.Copyright © 2023. Published by Elsevier Ltd.