Aldh3a2, also known as aldehyde dehydrogenase 3 family member A2, catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid [1,3]. It is involved in lipid metabolic, GSH metabolic, phospholipid metabolic, and aldehyde metabolic pathways [1]. In the context of various biological processes and diseases, its function is of great significance.

In ovarian cancer, knockout of Aldh3a2 increased the sensitivity of ovarian cancer cells to ferroptosis, while overexpression attenuated this sensitivity, suggesting its role in regulating ferroptosis-related cell survival [1]. In acute myeloid leukemia (AML), leukemic cells depended on Aldh3a2 to prevent cellular oxidative damage, and inhibition of Aldh3a2 was synthetically lethal with glutathione peroxidase-4 (GPX4) inhibition, which is a trigger of ferroptosis [3]. In clear cell renal cell carcinoma (ccRCC), miR-1182-mediated inhibition of Aldh3a2 affected lipid metabolism and tumor progression by activating the PI3K-AKT pathway [2].

In conclusion, Aldh3a2 is crucial in regulating lipid metabolism-related pathways and has a significant impact on the development and progression of several cancers, such as ovarian cancer, AML, and ccRCC. The gene knockout or knockdown studies in these disease models have revealed its role in ferroptosis regulation and lipid-associated tumorigenesis, providing potential therapeutic strategies for these malignancies [1,2,3].

References:

1. Dong, Hao, He, Linsheng, Sun, Qiran, Yin, Chen, He, Quan. 2023. Inhibit ALDH3A2 reduce ovarian cancer cells survival via elevating ferroptosis sensitivity. In Gene, 876, 147515. doi:10.1016/j.gene.2023.147515. https://pubmed.ncbi.nlm.nih.gov/37247796/

2. Lv, Qingyang, Shi, Jian, Miao, Daojia, Xiong, Zhiyong, Zhang, Xiaoping. 2023. miR-1182-mediated ALDH3A2 inhibition affects lipid metabolism and progression in ccRCC by activating the PI3K-AKT pathway. In Translational oncology, 40, 101835. doi:10.1016/j.tranon.2023.101835. https://pubmed.ncbi.nlm.nih.gov/38039946/

3. Yusuf, Rushdia Zareen, Saez, Borja, Sharda, Azeem, Rizzo, William B, Scadden, David T. . Aldehyde dehydrogenase 3a2 protects AML cells from oxidative death and the synthetic lethality of ferroptosis inducers. In Blood, 136, 1303-1316. doi:10.1182/blood.2019001808. https://pubmed.ncbi.nlm.nih.gov/32458004/