2. Academic Validation
  3. CDCA3-MYC positive feedback loop promotes bladder cancer progression via ENO1-mediated glycolysis

CDCA3-MYC positive feedback loop promotes bladder cancer progression via ENO1-mediated glycolysis

  • J Exp Clin Cancer Res. 2025 Feb 20;44(1):63. doi: 10.1186/s13046-025-03325-7.
Dexin Shen # 1,  Xiang Yu # 2,  Xuefeng Fan # 2,  Yu Liang # 2,  Dongmei Lu 3,  Zongpan Ke 4,  Lei Wang 2,  Ping Xiang 2,  Jun Xiao 5
Affiliations

Affiliations

  • 1 Department of Urology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China. mltyyds@ustc.edu.cn.
  • 2 Department of Urology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.
  • 3 Core Facility Center for Medical Sciences, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230001, China.
  • 4 Department of Urology, The Second Affiliated Hospital with Nanjing Medical University, Nanjing, China.
  • 5 Department of Urology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China. ixiaojun@ustc.edu.cn.
  • # Contributed equally.
PMID: 39980052 DOI: 10.1186/s13046-025-03325-7
Abstract

Background: Bladder Cancer (BLCA) ranks among the most prevalent malignancies of the urinary system, with its clinical diagnosis predominantly reliant on invasive procedures. Traditional chemotherapy regimens exhibit significant limitations, underscoring the urgency of identifying novel diagnostic biomarkers and strategies to enhance chemotherapy efficacy. CDCA3 has been recognized as a facilitator of BLCA progression, activated by MYBL2. However, its precise regulatory mechanisms in BLCA pathogenesis remain incompletely elucidated.

Methods: To investigate the functional role of CDCA3 in BLCA, MTT and colony formation assays were employed to assess cellular proliferation, while flow cytometry was utilized to evaluate Apoptosis and intracellular ROS levels. The expression of CDCA3, ENO1, TRIM28, and MYC was analyzed through WB and qRT-PCR, and Co-IP assays were conducted to delineate interactions among CDCA3, TRIM28, and MYC.

Results: CDCA3, a key regulator of the cell cycle, facilitates BLCA glycolysis by modulating the transcriptional expression of α-Enolase (ENO1), thereby enhancing BLCA progression. Mechanistically, CDCA3 recruits TRIM28, which stabilizes MYC, while MYC transcriptionally upregulates CDCA3, establishing a self-reinforcing CDCA3-MYC feedback loop. A risk prediction model incorporating the expression profiles of CDCA3 and ENO1 was developed to evaluate the overall survival of patients with BLCA. This model provides a prognostic tool to predict survival outcomes in patients with BLCA based on CDCA3 and ENO1 expression levels.

Conclusions: This study delineates a novel role for CDCA3 in the regulation of BLCA glycolysis and identifies its interaction with MYC as a critical positive feedback mechanism, providing fresh insights into the molecular mechanisms underlying BLCA progression.

Keywords

Bladder cancer; CDCA3; Glycolysis; MYC; TRIM28.

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