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Original Research

Open Access

Targeting CENPN to inhibit breast cancer progression: insights into cell growth and aerobic glycolysis modulation

  • Zhe Ye1
  • Qiuyan Lin2
  • Hualong Lin2
  • Yiwei Huang1,*,

1Department of Tumor Radiotherapy, The Third Affiliated Hospital of Wenzhou Medical University, 325200 Rui’an, Zhejiang, China

2Department of Oncology, The Third Affiliated Hospital of Wenzhou Medical University, 325200 Rui’an, Zhejiang, China

DOI: 10.22514/ejgo.2024.037 Vol.45,Issue 2,April 2024 pp.147-157

Submitted: 22 January 2024 Accepted: 18 March 2024

Published: 15 April 2024

*Corresponding Author(s): Yiwei Huang E-mail: yw_huang0711@163.com

Abstract

Breast cancer represents a significant health challenge for women globally. Although centromere protein N (CENPN) is reported to be upregulated in breast cancer, its detailed role remains unclear. This study used in silico analysis to investigate the expression profile and survival impact of CENPN in breast cancer. The CENPN level was evaluated using real-time quantitative polymerase chain reaction and western blot assays. The influence of CENPN on cell proliferation and aerobic glycolysis was investigated through cell counting kit-8, 5-ethynyl-2′-deoxyuridine incorporation assays, measurements of the extracellular acidification rate (ECAR), glucose uptake, lactate production, and additional western blot analyses. Moreover, in vivo studies on xenografted mice were conducted, utilizing immunohistochemistry and western blot techniques to evaluate the functions of CENPN. These findings revealed an upregulation of CENPN, correlating with decreased survival rates in breast cancer patients. Functionally, CENPN was shown to stimulate cell growth in both cell culture and animal models. Through gain- and loss-of-function experiments, CENPN was found to increase the ECAR, glucose uptake, lactate production, and the protein levels of glucose transporter 1 (GLUT1) and hexokinase 2 (HK2). Furthermore, CENPN was observed to increase the levels of phosphorylated protein kinase B (AKT) (p-AKT) relative to total AKT and hypoxia-inducible factor 1α (HIF-1α) in both cellular and animal models. The HIF-1α overexpression mitigated the suppressive effects of sh-CENPN on cell proliferation and aerobic glycolysis in breast cells. In conclusion, CENPN is upregulated and is related to a lower survival probability in breast cancer. It facilitates cell growth and aerobic glycolysis by upregulating AKT/HIF-1α signaling pathways. These insights provide novel perspectives for the diagnosis and treatment of breast cancer.


Keywords

Breast cancer; CENPN; Growth; Aerobic glycolysis; PI3K/AKT; HIF-1α


Cite and Share

Zhe Ye,Qiuyan Lin,Hualong Lin,Yiwei Huang. Targeting CENPN to inhibit breast cancer progression: insights into cell growth and aerobic glycolysis modulation. European Journal of Gynaecological Oncology. 2024. 45(2);147-157.

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