2. Academic Validation
  3. Inhibit ALDH3A2 reduce ovarian cancer cells survival via elevating ferroptosis sensitivity

Inhibit ALDH3A2 reduce ovarian cancer cells survival via elevating ferroptosis sensitivity

  • Gene. 2023 May 27;147515. doi: 10.1016/j.gene.2023.147515.
Hao Dong 1,  Linsheng He 1,  Qiran Sun 1,  Jiao Zhan 1,  Jiaqi Li 2,  Xiaoming Xiong 2,  Lingling Zhuang 3,  Shuqing Wu 3,  Yuan Li 4,  Chen Yin 5,  Quan He 6
Affiliations

Affiliations

  • 1 Department of Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
  • 2 Jiangxi Maternal and Child Health Hospital, Nanchang, 330006, China.
  • 3 Medical College, Nanchang University, Nanchang, 330006, China.
  • 4 Department of Gynecology, The First People's Hospital of Foshan, Foshan 528000, Guangdong, China.
  • 5 Department of Emergency, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
  • 6 Department of Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China. Electronic address: [email protected].
PMID: 37247796 DOI: 10.1016/j.gene.2023.147515
Abstract

Ovarian Cancer (OC) is a malignant gynecologic tumor with high morbidity and mortality. As a newly discovered mode of programmed cell death, Ferroptosis has been involved in various pathological processes of kinds of tumors in recent years. Aldehyde dehydrogenase 3 family member A2 (ALDH3A2) catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid. ALDH3A2 has been shown to be associated with Ferroptosis in acute myeloid leukemia (AML), but the mechanism remains unclear. In this study, we analyzed the TCGA and GTEx databases and showed that high ALDH3A2 expression predicted poor prognosis in ovarian Cancer. Further studies found that knockout or overexpression of ALDH3A2 correspondingly increased or attenuated the Ferroptosis sensitivity of ovarian Cancer cells. And sequencing revealed that ALDH3A2 knockout led to the activation of lipid metabolic, GSH metabolic, phospholipid metabolic, and aldehyde metabolic pathways, suggesting that ALDH3A2 induced changes in the sensitivity of ovarian Cancer cells to Ferroptosis by affecting these metabolic processes. Our results provide a new promising therapeutic strategy for the treatment of OC.

Keywords

Ferroptosis; GSH; RSL-3; lipid peroxide; ovarian cancer.

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