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.

中文翻译：

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FADS2 在主要癌症热点 11q13 位点的功能改变了癌症中的脂肪酸代谢


脂肪酸代谢失调和从头脂肪生成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） 信号转导前体（如花生四烯酸）。人类染色体 11q13 基因座长期以来已被确定为多种人类癌症中扩增最频繁的基因座。负责 HUFA 生物合成的脂肪酸去饱和酶基因 （FADS1、FADS2 和 FADS3） 位于 11q12-13.1 区域。FADS2 活性是混杂的，通过 Δ6、Δ8 和 Δ4 去饱和催化几种不饱和脂肪酸的生物合成。我们在这里的主要目的是回顾 FADS2 失调的已知和推定后果，这是由于对可能驱动各种癌症类型的 11q13 基因座的影响。FADS2 沉默导致 MCF7 细胞中 sciadonic acid （5Z，11Z，14Z-20：3） 的合成和体内乳腺癌的合成。5Z，11Z，14Z-20：3 在结构上与花生四烯酸 （5Z，8Z，11Z，14Z–20：4） 相同，但它缺乏合成前列腺素和白三烯等类花生酸所需的内部 Δ8 双键。棕榈酸对 SCD 和 FADS2 均具有底物特异性。对 SCD 抑制不敏感的黑色素瘤、前列腺癌、肝癌和肺癌细胞表现出 FADS2 活性和智能酸生物合成增加。在肝细胞癌患者中发现的血清蜂蜜酸水平升高表明对花生四烯酸的需求未得到满足。FADS2 环状 RNA 在结直肠癌和肺癌组织中处于高水平。FADS2 环状 RNA 与结直肠癌患者总生存期缩短相关。因此，证据支持未来研究 FADS2 在一系列肿瘤疾病中作为肿瘤抑制因子的作用。