2. Academic Validation
  3. Tau Aggregation-Dependent Lipid Peroxide Accumulation Driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau Complex Inhibits Epithelial Ovarian Cancer Peritoneal Metastasis

Tau Aggregation-Dependent Lipid Peroxide Accumulation Driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau Complex Inhibits Epithelial Ovarian Cancer Peritoneal Metastasis

  • Adv Sci (Weinh). 2024 Apr 18:e2310134. doi: 10.1002/advs.202310134.
BinShu Chai 1 2,  Yong Wu 3 4,  HengHui Yang 1,  BiaoFeng Fan 1,  SiYu Cao 4,  XiaoFei Zhang 5,  YaQing Xie 1,  ZhiXiang Hu 6,  ZhongLiang Ma 2,  YunKui Zhang 7,  Wei Pan 2,  Wei Meng 2,  Jiao Meng 3 8,  WenJuan Tian 4,  JiaLi Zhang 8,  YanLi Li 2,  Yang Shao 3 8,  ShaoJia Wang 1
Affiliations

Affiliations

  • 1 Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, China.
  • 2 Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai, 200444, China.
  • 3 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • 4 Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
  • 5 Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 2699 West Gaoke Road, Shanghai, 201204, China.
  • 6 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
  • 7 Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
  • 8 Cancer Institute, Fudan University Shanghai Cancer Center, and Shanghai Fifth People's Hospital, Shanghai, 200032, China.
PMID: 38634567 DOI: 10.1002/advs.202310134
Abstract

Intraperitoneal dissemination is the main method of epithelial ovarian Cancer (EOC) metastasis, which is related to poor prognosis and a high recurrence rate. Circular RNAs (circRNAs) are a novel class of endogenous RNAs with covalently closed loop structures that are implicated in the regulation of tumor development. In this study, hsa_circ_0001546 is downregulated in EOC primary and metastatic tissues vs. control tissues and this phenotype has a favorable effect on EOC OS and DFS. hsa_circ_0001546 can directly bind with 14-3-3 proteins to act as a chaperone molecule and has a limited positive effect on 14-3-3 protein stability. This complex recruits CAMK2D to induce the Ser324 phosphorylation of Tau proteins, changing the phosphorylation status of Tau bound to 14-3-3 and ultimately forming the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex. The existence of this complex stimulates the production of Tau aggregation, which then induces the accumulation of lipid peroxides (LPOs) and causes LPO-dependent Ferroptosis. In vivo, treatment with ferrostatin-1 and TRx0237 rescued the inhibitory effect of hsa_circ_0001546 on EOC cell spreading. Therefore, based on this results, Ferroptosis caused by Tau aggregation occurs in EOC cells, which is not only in Alzheimer's disease- or Parkinson's disease-related cells and this kind of Ferroptosis driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex is LPO-dependent rather than GPX4-dependent is hypothesized.

Keywords

14‐3‐3; Tau; epithelial ovarian cancer; ferroptosis; lipid peroxide.

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