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Peer-reviewedCC BY 4.0Frontiers in Oncology

The CP-STPG3-AS1 axis regulates lipoylation and cuproptosis in castration-resistant prostate cancer

  • Jia Wei He1
  • Pei Zhen Li2
  • Zhen Zhao Zhang3
  1. 1Department of Urology, The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University
  2. 2Department of Orthopedics, Dongguan Eighth People’s Hospital
  3. 3Department of Rehabilitation Medicine, The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University
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Abstract

Background: Prostate cancer (PCa), particularly metastatic castration-resistant PCa (mCRPC), remains therapeutically challenging. Cuproptosis, a copper-dependent cell death driven by lipoylated tricarboxylic acid cycle proteins, is implicated in PCa progression, but whether ceruloplasmin (CP), a key copper-binding glycoprotein, modulates cuproptosis in PCa and the underlying mediators remain unknown.

Methods: We integrated bioinformatic analysis of TCGA-PRAD data (550 PCa, 52 normal tissues) with in vitro validation in two androgen-independent CRPC cell lines: PC-3 cells received exogenous CP gradients, while 22Rv1 cells underwent CP knockdown and rescue experiments with qPCR, Western blot, MitoSOX flow cytometry, and CCK-8 assays.

Results: Eighty CP-cuproptosis intersection genes were identified. Cuproptosis core genes (FDX1, DLST, LIAS, DLD) were significantly upregulated in PCa (all p<0.001), while CP showed no differential expression but weak positive correlations with these genes (r=0.205-0.300). Exogenous CP concentration-dependently reduced PC-3 metabolic activity and induced apoptosis-related morphology. In 22Rv1 cells, CP knockdown downregulated lncRNA STPG3-AS1, upregulated cuproptosis-related markers (FDX1, DLAT, lipoylated proteins) and mitochondrial ROS, and inhibited proliferation; STPG3-AS1 overexpression reversed all these effects. No gene showed independent prognostic value.

Conclusion: STPG3-AS1 mediates CP-regulated lipoylation and cuproptosis-associated molecular changes in CRPC cells, identifying a novel CP-STPG3-AS1-cuproptosis regulatory axis with therapeutic potential for advanced prostate cancer.

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Cite

BibTeXRIS
BibTeX
@article{he2026cpstpg3as1,
  title = {{The CP-STPG3-AS1 axis regulates lipoylation and cuproptosis in castration-resistant prostate cancer}},
  author = {Jia Wei He and Pei Zhen Li and Zhen Zhao Zhang},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1989277},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1989277/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The CP-STPG3-AS1 axis regulates lipoylation and cuproptosis in castration-resistant prostate cancer
AU  - Jia Wei He
AU  - Pei Zhen Li
AU  - Zhen Zhao Zhang
PY  - 2026
DA  - 2026/10/22
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1989277
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1989277/full
AB  - Background: Prostate cancer (PCa), particularly metastatic castration-resistant PCa (mCRPC), remains therapeutically challenging. Cuproptosis, a copper-dependent cell death driven by lipoylated tricarboxylic acid cycle proteins, is implicated in PCa progression, but whether ceruloplasmin (CP), a key copper-binding glycoprotein, modulates cuproptosis in PCa and the underlying mediators remain unknown.  Methods: We integrated bioinformatic analysis of TCGA-PRAD data (550 PCa, 52 normal tissues) with in vitro validation in two androgen-independent CRPC cell lines: PC-3 cells received exogenous CP gradients, while 22Rv1 cells underwent CP knockdown and rescue experiments with qPCR, Western blot, MitoSOX flow cytometry, and CCK-8 assays.  Results: Eighty CP-cuproptosis intersection genes were identified. Cuproptosis core genes (FDX1, DLST, LIAS, DLD) were significantly upregulated in PCa (all p<0.001), while CP showed no differential expression but weak positive correlations with these genes (r=0.205-0.300). Exogenous CP concentration-dependently reduced PC-3 metabolic activity and induced apoptosis-related morphology. In 22Rv1 cells, CP knockdown downregulated lncRNA STPG3-AS1, upregulated cuproptosis-related markers (FDX1, DLAT, lipoylated proteins) and mitochondrial ROS, and inhibited proliferation; STPG3-AS1 overexpression reversed all these effects. No gene showed independent prognostic value.  Conclusion: STPG3-AS1 mediates CP-regulated lipoylation and cuproptosis-associated molecular changes in CRPC cells, identifying a novel CP-STPG3-AS1-cuproptosis regulatory axis with therapeutic potential for advanced prostate cancer.
SN  - 2234-943X
ER  -