ACADSB, also known as short/branched chain acyl-CoA dehydrogenase, is a member of the acyl-CoA dehydrogenase gene family. It functions in the metabolism of fatty acids and branched-chain amino acids, oxidizing short branched-chain and short straight-chain acyl-CoA derivatives [5]. Its activity is crucial for normal cellular metabolism and is associated with pathways like fatty acid metabolism, branched-chain amino acid metabolism, and iron regulation [2].

In cancer research, ACADSB shows potential significance. In colorectal cancer, its low expression in tissues is negatively correlated with N-and M-stage CRC, yet positively with overall survival rate. Overexpression inhibits cell migration, invasion, and proliferation, likely by negatively regulating glutathione-related enzymes and enhancing ferroptosis-related indicators [1]. In clear cell renal cell carcinoma, its down-regulation is associated with high tumor stage and grade, and is an independent risk factor for overall survival. Pan-cancer analysis shows its down-regulation in multiple cancers, and its expression is positively correlated with ferroptosis driver genes [2]. In gastric cancer, a tRNA-derived fragment promotes cancer progression by targeting ACADSB, and down-regulated ACADSB may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis [3]. In non-small cell lung cancer, a polymorphism in ACADSB is associated with better survival outcome, and the variant allele increases promoter activity [4].

Overall, ACADSB is important for fatty acid and branched-chain amino acid metabolism. Its study in cancer models reveals its potential role in regulating cancer cell behavior, especially in relation to ferroptosis, lipid metabolism, and patient prognosis. These findings provide insights into its function and offer potential therapeutic targets in cancer treatment [1,2,3,4].

References:

1. Lu, Di, Yang, Zhiyu, Xia, Qiaoyun, Zhang, XiuLei, Li, Xiuling. 2020. ACADSB regulates ferroptosis and affects the migration, invasion, and proliferation of colorectal cancer cells. In Cell biology international, 44, 2334-2343. doi:10.1002/cbin.11443. https://pubmed.ncbi.nlm.nih.gov/32776663/

2. Liu, Xianhui, Zhang, Weiyu, Wang, Huanrui, Zhu, Lin, Xu, Kexin. 2022. Decreased Expression of ACADSB Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma. In Frontiers in oncology, 11, 762629. doi:10.3389/fonc.2021.762629. https://pubmed.ncbi.nlm.nih.gov/35096573/

3. Zhang, Yu, Gu, Xinliang, Li, Yang, Huang, Yuejiao, Ju, Shaoqing. . Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB. In Journal of Zhejiang University. Science. B, 25, 438-450. doi:10.1631/jzus.B2300215. https://pubmed.ncbi.nlm.nih.gov/38725342/

4. Yoo, Seung Soo, Do, Sook Kyung, Choi, Jin Eun, Kim, Chang Ho, Park, Jae Yong. 2023. Lipid Metabolism Pathway Genes and Lung Cancer: ACADSB rs12220683G>C Is Associated with Better Survival Outcome in Patients with Non-Small Cell Lung Cancer. In Oncology, 102, 67-75. doi:10.1159/000533156. https://pubmed.ncbi.nlm.nih.gov/37527640/

5. Rozen, R, Vockley, J, Zhou, L, Torban, E, Fournier, B. . Isolation and expression of a cDNA encoding the precursor for a novel member (ACADSB) of the acyl-CoA dehydrogenase gene family. In Genomics, 24, 280-7. doi:. https://pubmed.ncbi.nlm.nih.gov/7698750/