2. Academic Validation
  3. Squalene epoxidase promotes breast cancer progression by regulating CCNB1 protein stability

Squalene epoxidase promotes breast cancer progression by regulating CCNB1 protein stability

  • Exp Cell Res. 2023 Oct 13:113805. doi: 10.1016/j.yexcr.2023.113805.
Dilihumaer Tuluhong 1,  Hongyu Gao 1,  Xinfang Li 1,  Lulu Wang 2,  Yueyun Zhu 2,  Cheng Xu 2,  Jingjie Wang 2,  Hanjun Li 2,  Qiurong Li 3,  Shaohua Wang 4
Affiliations

Affiliations

  • 1 Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, Jiangsu, 210002, China.
  • 2 Department of General Surgery, Women`s Hospital of Nanjing Medical University. Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, 210004, China.
  • 3 Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, Jiangsu, 210002, China. Electronic address: liqiurongjue@126.com.
  • 4 Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, Jiangsu, 210002, China; Department of General Surgery, Women`s Hospital of Nanjing Medical University. Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, 210004, China. Electronic address: wangsh_jinling@126.com.
PMID: 37839786 DOI: 10.1016/j.yexcr.2023.113805
Abstract

Background: Breast Cancer (BC) is a prevalent malignancy affecting women, characterized by a substantial occurrence rate. Squalene epoxidase (SQLE) is a crucial regulator of Ferroptosis and has been associated with promoting cell growth and invasion in different types of human cancers. This study aimed to investigate the functional significance of SQLE in BC and elucidate the underlying molecular mechanisms involved.

Methods: SQLE expression levels in BC tissues were evaluated using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. Cell viability, invasion, migration, and cell cycle distribution were assessed using a combination of assays, including the Cell Counting Kit-8, EdU, colony formation, Transwell, and wound healing assays and flow cytometry analysis. Measurement of intracellular Reactive Oxygen Species (ROS), malondialdehyde assay, and glutathione assay were utilized to investigate Ferroptosis. Furthermore, co-immunoprecipitation and immunofluorescence assays were conducted to explore the correlation between SQLE and CCNB1. The in vivo tumor growth was evaluated by conducting a xenograft tumorigenicity assay to investigate the impact of SQLE.

Results: SQLE expression was significantly increased in BC, and higher SQLE expression levels were significantly associated with an unfavorable prognosis. In vitro functional assays revealed that the overexpression of SQLE markedly enhanced the proliferation, migration, and invasion capacities of BC cells. Furthermore, SQLE overexpression facilitated tumor growth in nude mice. Mechanistically, SQLE alleviated the ubiquitination modification of CCNB1, leading to enhanced stability of the CCNB1 protein and decreased intracellular ROS levels. Ultimately, this inhibited Ferroptosis and facilitated the progression of BC. Our findings have provided insights into a crucial pathway by which elevated SQLE expression confers protection to BC cells against Ferroptosis, thus promoting Cancer progression. SQLE may serve as a novel oncological marker and a potential therapeutic target for BC progression.

Conclusions: In conclusion, this study provides evidence that SQLE plays a regulatory role in BC progression by modulating CCNB1 and Ferroptosis. These findings offer valuable insights into the role of SQLE in the pathogenesis of BC and demonstrate its potential as a therapeutic target for treating BC.

Keywords

Breast cancer; CCNB1; Ferroptosis; Prognosis; SQLE.

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