Aldh3a1, aldehyde dehydrogenase 3A1, is an NAD+-dependent enzyme. It is involved in various biological functions such as metabolism of toxic aldehydes, generation of antioxidant NADPH, and has chaperone-like activity. In the cornea, it protects against UV-induced oxidative stress and may contribute to the optical properties of the cornea. It also seems to play a role in cell cycle regulation [3].

In non-small-cell lung cancer (NSCLC), hypoxia-induced Aldh3a1 promotes cell proliferation by enhancing glycolysis and suppressing oxidative phosphorylation through the HIF-1α/LDHA pathway. It is highly expressed in NSCLC tissue, especially in late-stage patients, and is associated with a poor prognosis. β-elemene can downregulate Aldh3a1 to inhibit NSCLC proliferation [1]. In lung adenocarcinoma, Aldh3a1 drives tumor metastasis through the p53/BAG1 axis, and its high expression predicts a poor prognosis. Knockdown of Aldh3a1 decreases cell proliferation, migration, and invasion [4]. In oral squamous cell carcinoma (OSCC), Aldh3a1 is significantly reduced. Its overexpression suppresses tumorigenesis by inhibiting neutrophils N2 polarization through the PI3K/AKT/NF-κB pathway, and it also inhibits inflammation via phospho-Ser727 at STAT3 in tumor-associated macrophages. Additionally, restored Aldh3a1 expression suppresses OSCC cell proliferation, migration, and invasion by inhibiting epithelial-mesenchymal transition through the IL-6/STAT3 signaling pathway [2,5,6].

In conclusion, Aldh3a1 is involved in multiple biological processes and has significant implications in cancer. Studies on Aldh3a1, especially through loss-of-function experiments in cancer cell lines, have revealed its role in promoting tumor growth, metastasis, and inflammation in NSCLC, lung adenocarcinoma, and OSCC, providing potential therapeutic targets for these diseases.

References:

1. Chen, Yang, Yan, Hongfei, Yan, Lirong, Zhang, Ye, Hu, Xuejun. 2023. Hypoxia-induced ALDH3A1 promotes the proliferation of non-small-cell lung cancer by regulating energy metabolism reprogramming. In Cell death & disease, 14, 617. doi:10.1038/s41419-023-06142-y. https://pubmed.ncbi.nlm.nih.gov/37730658/

2. He, Ying, Qu, Yi, Jin, Shan, Zhang, Yongfeng, Qin, Lizheng. 2024. ALDH3A1 upregulation inhibits neutrophils N2 polarization and halts oral cancer growth. In Oral diseases, 30, 4231-4242. doi:10.1111/odi.14863. https://pubmed.ncbi.nlm.nih.gov/38225738/

3. Estey, Tia, Piatigorsky, Joram, Lassen, Natalie, Vasiliou, Vasilis. 2006. ALDH3A1: a corneal crystallin with diverse functions. In Experimental eye research, 84, 3-12. doi:. https://pubmed.ncbi.nlm.nih.gov/16797007/

4. Fan, Feifei, Yin, Ruxue, Wang, Liuya, Zhang, Xiaohong, Wang, Hongmin. 2021. ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma. In Journal of Cancer, 12, 4780-4790. doi:10.7150/jca.58250. https://pubmed.ncbi.nlm.nih.gov/34234849/

5. Wang, Boyuan, He, Ying, Wang, Bin, Li, Jing, Qin, Lizheng. 2022. ALDH3A1 overexpression in OSCC inhibits inflammation via phospho-Ser727 at STAT3 in tumor-associated macrophages. In Oral diseases, 29, 1513-1524. doi:10.1111/odi.14161. https://pubmed.ncbi.nlm.nih.gov/35188323/

6. Qu, Yi, He, Ying, Yang, Yang, Han, Zhengxue, Qin, Lizheng. 2020. ALDH3A1 acts as a prognostic biomarker and inhibits the epithelial mesenchymal transition of oral squamous cell carcinoma through IL-6/STAT3 signaling pathway. In Journal of Cancer, 11, 2621-2631. doi:10.7150/jca.40171. https://pubmed.ncbi.nlm.nih.gov/32201532/