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.

通过花生四烯酸等高度不饱和脂肪酸 (HUFA) 信号前体，脂肪酸代谢和从头脂肪生成失调是多种癌症类型的关键驱动因素。人类染色体 11q13 基因座早已被确定为在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）定位于 11q12-13.1 区域。FADS2 活性是混杂的，通过 Δ6、Δ8 和 Δ4 去饱和催化多种不饱和脂肪酸的生物合成。我们在此的主要目的是回顾 FADS2 失调由于对 11q13 位点的影响而可能导致各种癌症类型的已知和推定的后果。FADS2 沉默会导致 MCF7 细胞和体内乳腺癌合成 sciadonic 酸 (5Z,11Z,14Z-20:3) 。5Z,11Z,14Z-20:3 在结构上与花生四烯酸 (5Z,8Z,11Z,14Z–20:4) 相同，只是它缺少前列腺素和白三烯合成以及其他类二十烷酸所需的内部 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、肝癌和肺癌细胞显示 FADS2 活性和 sapienic 酸生物合成增加。肝细胞癌患者血清米德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 与结直肠癌患者的总生存期较短有关。迄今为止的证据支持未来研究 FADS2 作为肿瘤抑制因子在一系列肿瘤性疾病中的作用。