2. Academic Validation
  3. Activation of the FOXM1/ASF1B/PRDX3 axis confers hyperproliferative and antioxidative stress reactivity to gastric cancer

Activation of the FOXM1/ASF1B/PRDX3 axis confers hyperproliferative and antioxidative stress reactivity to gastric cancer

  • Cancer Lett. 2024 Mar 26:589:216796. doi: 10.1016/j.canlet.2024.216796.
Zhou Zhao 1,  Zhaolun Cai 2,  Su Zhang 3,  Xiaonan Yin 2,  Tianxiang Jiang 2,  Chaoyong Shen 2,  Yuan Yin 2,  Hao Sun 4,  Zhixin Chen 2,  Junhong Han 5,  Bo Zhang 6
Affiliations

Affiliations

  • 1 Gastric Cancer Center, Department of General Surgery, Research Laboratory of Tumor Epigenetics and Genomics, West China Hospital, Sichuan University, Chengdu, China; Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China.
  • 2 Gastric Cancer Center, Department of General Surgery, Research Laboratory of Tumor Epigenetics and Genomics, West China Hospital, Sichuan University, Chengdu, China.
  • 3 State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
  • 4 Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China.
  • 5 State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China. Electronic address: hjunhong@scu.edu.cn.
  • 6 Gastric Cancer Center, Department of General Surgery, Research Laboratory of Tumor Epigenetics and Genomics, West China Hospital, Sichuan University, Chengdu, China. Electronic address: zhangbo_scu@scu.edu.cn.
PMID: 38537775 DOI: 10.1016/j.canlet.2024.216796
Abstract

Nucleosome assembly during DNA replication is dependent on histone chaperones. Recent studies suggest that dysregulated histone chaperones contribute to Cancer progression, including gastric Cancer (GC). Further studies are required to explore the prognostic and therapeutic implications of histone chaperones and their mechanisms of action in GC progression. Here we identified histone chaperone ASF1B as a potential biomarker for GC proliferation and prognosis. ASF1B was significantly upregulated in GC, which was associated with poor prognosis. In vitro and in vivo experiments demonstrated that the inhibition of ASF1B suppressed the malignant characteristics of GC, while overexpression of ASF1B had the opposite effect. Mechanistically, transcription factor FOXM1 directly bound to the ASF1B-promoter region, thereby regulating its transcription. Treatment with thiostrepton, a FOXM1 inhibitor, not only suppressed ASF1B expression, but also inhibited GC progression. Furthermore, ASF1B regulated the mitochondrial protein peroxiredoxin 3 (PRDX3) transcription in a FOXM1-dependent manner. The crucial role of ASF1B-regulated PRDX3 in GC cell proliferation and oxidative stress balance was also elucidated. In summary, our study suggests that the FOXM1-ASF1B-PRDX3 axis is a potential therapeutic target for treating GC.

Keywords

ASF1B; FOXM1; Gastric cancer; Oxidative stress; PRDX3.

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