Hypoxia-induced ALDH3A1 promotes the proliferation of non-small-cell lung cancer by regulating energy metabolism reprogramming

Autor: Yang Chen, Hongfei Yan, Lirong Yan, Ximing Wang, Xiaofang Che, Kezuo Hou, Yi Yang, Xuena Li, Yaming Li, Ye Zhang, Xuejun Hu
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Death and Disease, Vol 14, Iss 9, Pp 1-11 (2023)
Druh dokumentu: article
ISSN: 2041-4889
DOI: 10.1038/s41419-023-06142-y
Popis: Abstract Aldehyde dehydrogenase 3A1 (ALDH3A1) is an NAD+-dependent enzyme that is closely related to tumor development. However, its role in non-small-cell lung cancer (NSCLC) has not been elucidated. This study aimed to clarify the mechanism of ALDH3A1 and identify potential therapeutic targets for NSCLC. Here, for the first time, we found that ALDH3A1 expression could be induced by a hypoxic environment in NSCLC. ALDH3A1 was highly expressed in NSCLC tissue, especially in some late-stage patients, and was associated with a poor prognosis. In mechanistic terms, ALDH3A1 enhances glycolysis and suppresses oxidative phosphorylation (OXPHOS) to promote cell proliferation by activating the HIF-1α/LDHA pathway in NSCLC. In addition, the results showed that ALDH3A1 was a target of β-elemene. ALDH3A1 can be downregulated by β-elemene to inhibit glycolysis and enhance OXPHOS, thus suppressing NSCLC proliferation in vitro and in vivo. In conclusion, hypoxia-induced ALDH3A1 is related to the energy metabolic status of tumors and the efficacy of β-elemene, providing a new theoretical basis for better clinical applications in NSCLC.
Databáze: Directory of Open Access Journals