Lipid metabolism reprogram plays key roles in breast cancer tumorigenesis and immune escape. The underlying mechanism and potential regulator were barely investigated. We thus established an in vivo tumorigenesis model, mice-bearing breast cancer cells were treated with an ordinary diet and high-fat diet, species were collected and subjected to circRNA sequence to scan the potential circRNAs regulating the lipid metabolism. CircSpdyA was one of the most upregulated circRNAs and had the potential to encode a 127-aa micro peptide (referred to as 127aa). 127 aa promotes tumorigenesis through promoting the fatty acid de novo synthesis by directly binding to FASN. Single-cell sequence indicated 127aa inhibited NK cell infiltration and function. This was achieved by inhibiting the transcription of NK cell activators epigenetically. Moreover, lipid-laden from 127aa positive cancer cells transferred to NK cells inhibited the cytotoxicity. Taken together, circSpdyA encoded 127aa promotes fatty acid de novo synthesis through directly binding with FASN and induced NK cell repression by inhibiting the transcription of NK cell activators.

脂质代谢重编程在乳腺癌肿瘤发生和免疫逃逸中起关键作用。几乎没有研究其潜在机制和潜在调节因子。因此，我们建立了体内肿瘤发生模型，用普通饮食和高脂肪饮食处理小鼠荷瘤细胞，收集物种并进行 circRNA 序列扫描调节脂质代谢的潜在 circRNA。CircSpdyA 是上调最严重的 circRNA 之一，具有编码 127-aa 微肽（称为 127aa）的潜力。127 aa 通过直接与 FASN 结合促进脂肪酸从头合成来促进肿瘤发生。单细胞序列表明 127aa 抑制 NK 细胞浸润和功能。这是通过表观遗传抑制 NK 细胞激活剂的转录来实现的。此外，从 127aa 阳性癌细胞转移到 NK 细胞的满脂细胞抑制了细胞毒性。综上所述，circSpdyA 编码的 127aa 通过与 FASN 直接结合促进脂肪酸从头合成，并通过抑制 NK 细胞激活剂的转录诱导 NK 细胞抑制。