AOX1, also known as aldehyde oxidase 1, is involved in retinol metabolism [2]. It has been associated with various biological processes and disease conditions. In the context of methylotrophic yeast Pichia pastoris, the promoter of the alcohol oxidase gene I (AOX1) is widely used for recombinant protein production. This promoter is induced by methanol and repressed by glucose and ethanol [1,4].

In liver fibrosis, knockout of Sema4D alleviated the condition by suppressing AOX1 expression in retinol metabolism. This suggests AOX1 may play a role in promoting liver fibrosis [2]. In periodontal disease, AOX1 silencing in human periodontal ligament stem cells (hPDLMSCs) enhanced their osteogenic potential, indicating its involvement in regulating osteoblastogenesis [3]. In cancer research, AOX1 was identified as a biomarker for clear cell renal cell carcinoma (ccRCC), with higher expression predicting better overall survival. Also, in prostate cancer, low AOX1 expression promoted cell migration and invasion, and DNA methylation was associated with its down-regulation [5,6]. In pediatric papillary thyroid carcinoma, AOX1 expression was downregulated, and low levels were associated with poor survival, suggesting it could be a biomarker for diagnosis and prognosis [7].

In summary, AOX1 is involved in multiple biological processes such as retinol metabolism, osteoblastogenesis, and is associated with various diseases including liver fibrosis, different types of cancers. Studies, especially those involving gene knockout-like approaches in relevant models, have revealed its potential roles in disease development and progression, providing insights for potential therapeutic targets and diagnostic biomarkers.

References:

1. Türkanoğlu Özçelik, Aysun, Yılmaz, Semiramis, Inan, Mehmet. . Pichia pastoris Promoters. In Methods in molecular biology (Clifton, N.J.), 1923, 97-112. doi:10.1007/978-1-4939-9024-5_3. https://pubmed.ncbi.nlm.nih.gov/30737736/

2. Wang, Lifu, Li, Dinghao, Zhu, Zifeng, Wu, Zhongdao, Sun, Xi. 2023. Knockout of Sema4D alleviates liver fibrosis by suppressing AOX1 expression. In Pharmacological research, 195, 106886. doi:10.1016/j.phrs.2023.106886. https://pubmed.ncbi.nlm.nih.gov/37591326/

3. Sun, Shiwei, Iwata, Takanori. 2024. Role of AOX1 on RXR signaling regulates osteoblastogenesis in hPDLMSCs. In Scientific reports, 14, 16767. doi:10.1038/s41598-024-68009-2. https://pubmed.ncbi.nlm.nih.gov/39034354/

4. Mastropietro, Giuliana, Aw, Rochelle, Polizzi, Karen M. 2021. Expression of proteins in Pichia pastoris. In Methods in enzymology, 660, 53-80. doi:10.1016/bs.mie.2021.07.004. https://pubmed.ncbi.nlm.nih.gov/34742398/

5. Xiong, Luyang, Feng, Yuchen, Hu, Wei, Li, Shusheng, Wang, Hongjie. 2021. Expression of AOX1 Predicts Prognosis of Clear Cell Renal Cell Carcinoma. In Frontiers in genetics, 12, 683173. doi:10.3389/fgene.2021.683173. https://pubmed.ncbi.nlm.nih.gov/34290740/

6. Wu, Jinfeng, Wei, Yongbao, Li, Tao, Yang, Zesong, Ye, Liefu. 2022. DNA Methylation-Mediated Lowly Expressed AOX1 Promotes Cell Migration and Invasion of Prostate Cancer. In Urologia internationalis, 107, 517-525. doi:10.1159/000522634. https://pubmed.ncbi.nlm.nih.gov/35354150/

7. Yu, Yongbo, Wang, Shengcai, Zhang, Xuexi, Guo, Yongli, Ni, Xin. . Clinical implications of TPO and AOX1 in pediatric papillary thyroid carcinoma. In Translational pediatrics, 10, 723-732. doi:10.21037/tp-20-301. https://pubmed.ncbi.nlm.nih.gov/34012822/