2. Academic Validation
  3. Hypoxia-induced ALDH3A1 promotes the proliferation of non-small-cell lung cancer by regulating energy metabolism reprogramming

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

  • Cell Death Dis. 2023 Sep 20;14(9):617. doi: 10.1038/s41419-023-06142-y.
Yang Chen # 1 2,  Hongfei Yan # 3 4,  Lirong Yan 5,  Ximing Wang 1,  Xiaofang Che 3 4 6,  Kezuo Hou 3 4 6,  Yi Yang 7,  Xuena Li 8,  Yaming Li 8,  Ye Zhang 9,  Xuejun Hu 10
Affiliations

Affiliations

  • 1 Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, 110001, Shenyang, China.
  • 2 Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China.
  • 3 Department of Medical Oncology, The First Hospital of China Medical University, 110001, Shenyang, China.
  • 4 Key laboratory of anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, 110001, Shenyang, China.
  • 5 The First Laboratory of Cancer Institute, The First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, 110001, Shenyang, China.
  • 6 Liaoning Province Clinical Research Center for Cancer, 110001, Shenyang, China.
  • 7 Laboratory Animal Center, China Medical University, 110001, Shenyang, China.
  • 8 Department of Nuclear Medicine, The First Hospital of China Medical University, 110001, Shenyang, China.
  • 9 The First Laboratory of Cancer Institute, The First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, 110001, Shenyang, China. zhangyecmu@163.com.
  • 10 Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, 110001, Shenyang, China. xjhu@cmu.edu.cn.
  • # Contributed equally.
PMID: 37730658 DOI: 10.1038/s41419-023-06142-y
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.

Figures
Products