Mol Cancer Res. 2023 Jul 06. pii: MCR-22-0781. [Epub ahead of print]
Shenghua Zhang,
Zheng Zhang,
Xiaolong Liu,
Yibin Deng,
Jian Zheng,
Jieqiong Deng,
Yirong Wang,
Binbin Guo,
Fanrong Li,
Xiaoyue Chen,
Yacheng Pan,
Jieyu Wang,
Jiachun Lu,
Siqi Wu,
Qiang Guo,
Yifeng Zhou.
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. Implications: 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.