Zhang Shenghua, Zhang Zheng, Liu Xiaolong, Deng Yibin, Zheng Jian, Deng Jieqiong, Wang Yirong, Guo Binbin, Li Fanrong, Chen Xiaoyue, Pan Yacheng, Wang Jieyu, Lu Jiachun, Wu Siqi, Guo Qiang, Zhou Yifeng
Department of Genetics, Medical College of Soochow University, Suzhou, Jiangsu, China.
Institute of Critical Care Medicine, Dushu Lake Hospital Affiliated to Soochow University (Suzhou Dushu Lake Hospital); Medical College of Soochow University, Suzhou, Jiangsu, China.
Mol Cancer Res. 2023 Oct 2;21(10):1064-1078. doi: 10.1158/1541-7786.MCR-22-0781.
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of lethal kidney cancer. Reprogramming of fatty acid and glucose metabolism resulting in the accumulation of lipids and glycogen in the cytoplasm is a hallmark of ccRCC. Here, we identified a micropeptide ACLY-BP encoded by the GATA3-suppressed LINC00887, which regulated lipid metabolism and promoted cell proliferation and tumor growth in ccRCC. Mechanistically, the ACLY-BP stabilizes the ATP citrate lyase (ACLY) by maintaining ACLY acetylation and preventing ACLY from ubiquitylation and degradation, thereby leading to lipid deposition in ccRCC and promoting cell proliferation. Our results may offer a new clue for the therapeutic approaches and the diagnostic assessment for ccRCC.
This study identifies ACLY-BP encoded by LINC00887 as a lipid-related micropeptide that stabilizes ACLY to generate acetyl-CoA, driving lipid deposition and promoting cell proliferation in ccRCC.
透明细胞肾细胞癌（ccRCC）是致命性肾癌最常见的亚型。脂肪酸和葡萄糖代谢重编程导致细胞质中脂质和糖原积累是ccRCC的一个标志。在此，我们鉴定了一种由GATA3抑制的LINC00887编码的微小肽ACLY - BP，其在ccRCC中调节脂质代谢并促进细胞增殖和肿瘤生长。机制上，ACLY - BP通过维持ACLY乙酰化并防止ACLY泛素化和降解来稳定ATP柠檬酸裂解酶（ACLY），从而导致ccRCC中的脂质沉积并促进细胞增殖。我们的结果可能为ccRCC的治疗方法和诊断评估提供新线索。
本研究鉴定出由LINC00887编码的ACLY - BP作为一种与脂质相关的微小肽，其稳定ACLY以生成乙酰辅酶A，驱动ccRCC中的脂质沉积并促进细胞增殖。
