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  3. Targeting PRDX2 to inhibit tumor growth and metastasis in triple-negative breast cancer: the role of FN1 and the PI3K/AKT/SP1 pathway

Targeting PRDX2 to inhibit tumor growth and metastasis in triple-negative breast cancer: the role of FN1 and the PI3K/AKT/SP1 pathway

  • J Transl Med. 2025 Apr 11;23(1):434. doi: 10.1186/s12967-025-06441-2.
Jiawei Zhou 1 2 3,  Anqi Cheng 1 2,  Jianqiang Guo 1 2,  Yafeng Liu 1 2,  Xuan Li 1 2,  Maoqian Chen 1 2,  Dong Hu 4 5 6 7 8 9 10,  Jing Wu 11 12 13 14 15
Affiliations

Affiliations

  • 1 School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, 232000, China.
  • 2 School of Medicine, The First Affiliated Hospital of Anhui University of Science and Technology Huainan First People's Hospital, Huainan, Anhui, 232000, China.
  • 3 Department of Laboratory Medicine, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 232001, China.
  • 4 School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, 232000, China. dhu@aust.edu.cn.
  • 5 School of Medicine, The First Affiliated Hospital of Anhui University of Science and Technology Huainan First People's Hospital, Huainan, Anhui, 232000, China. dhu@aust.edu.cn.
  • 6 Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, 232000, China. dhu@aust.edu.cn.
  • 7 Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Huainan, Anhui, 232000, China. dhu@aust.edu.cn.
  • 8 Key Laboratory of Industrial Dust Prevention and Control & Occupational Safety and Health of the Ministry of Education, Anhui University of Science and Technology, Huainan, Anhui, 232000, China. dhu@aust.edu.cn.
  • 9 Department of Laboratory Medicine, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 232001, China. dhu@aust.edu.cn.
  • 10 , 168 Taifeng Street, Huainan, 232001, China. dhu@aust.edu.cn.
  • 11 School of Medicine, The First Affiliated Hospital of Anhui University of Science and Technology Huainan First People's Hospital, Huainan, Anhui, 232000, China. aust_jingwu@aust.edu.cn.
  • 12 Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, 232000, China. aust_jingwu@aust.edu.cn.
  • 13 Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Huainan, Anhui, 232000, China. aust_jingwu@aust.edu.cn.
  • 14 Key Laboratory of Industrial Dust Prevention and Control & Occupational Safety and Health of the Ministry of Education, Anhui University of Science and Technology, Huainan, Anhui, 232000, China. aust_jingwu@aust.edu.cn.
  • 15 Department of Laboratory Medicine, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 232001, China. aust_jingwu@aust.edu.cn.
PMID: 40217291 DOI: 10.1186/s12967-025-06441-2
Abstract

Background: Triple-negative breast Cancer (TNBC) is characterized by high invasiveness, high potential for metastasis, easy recurrence, and poor prognosis. There is an urgent need to develop new clinical treatments.

Methods: This study utilized TNBC tissue microarrays to detect Peroxiredoxin 2 (PRDX2) expression levels and analyzed the correlation between PRDX2 and tumor invasion as well as invasion-related gene expression through the TCGA database. A stable PRDX2-knockdown triple-negative breast Cancer cell line was established using lentiviral technology. The effects of PRDX2 on triple-negative breast Cancer cell migration, invasion, and epithelial-mesenchymal transition (EMT) were investigated via wound healing assays, Transwell assays, qPCR, and Western blotting. RNA Sequencing (RNA-seq), Western blotting, and dual luciferase reporter assays were performed to confirm that PRDX2 regulates FN1 expression through SP1. Furthermore, subcutaneous tumor xenograft models in nude mice were constructed to assess the effects of PRDX2 knockdown and the PRDX2 inhibitor Conoidin A on tumor growth in vivo.

Results: Tissue microarray detection and correlative analysis revealed that PRDX2 is significantly upregulated in triple-negative breast Cancer (TNBC) tumor tissues and positively correlated with genes associated with cell migration and invasion. Functional experiments demonstrated that in vitro knockdown of PRDX2 suppresses migration, invasion, and epithelial-mesenchymal transition (EMT) in TNBC cells. Furthermore, in vivo knockdown of PRDX2 or treatment with the PRDX2 inhibitor Conoidin A effectively reduced tumor burden. Mechanistic investigations utilizing RNA Sequencing (RNA-seq) identified FN1 as a critical gene promoting TNBC cell migration and invasion. PRDX2 facilitates TNBC progression by activating the PI3K/Akt signaling pathway, which enhances SP1 binding to the FN1 gene promoter. This regulatory cascade ultimately drives tumor advancement in TNBC.

Conclusions: This study elucidates the role of the PRDX2/SP1/FN1 axis in TNBC migration and invasion, and highlights PRDX2 as a promising therapeutic target for triple-negative breast Cancer.

Keywords

Cell migration and invasion; PI3K/AKT; PRDX2; SP1; TNBC.

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