The SP4–NUPR1–SELM Axis Promotes Glycolytic Reprogramming and Stemness-Associated Phenotypes in Bladder Cancer
- 1Department of Urology & Urology Laboratory, The Third Affiliated Hospital of Nanjing Medical University, Changzhou 213003, China
- 2Department of Physiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China
- 3Department of Radiology, The Third Affiliated Hospital of Nanjing Medical University, Changzhou 213003, China
Abstract
Background: Metabolic adaptation and stemness-associated programs contribute to bladder cancer growth. This study investigated the regulatory and functional relationships among specificity protein 4 (SP4), nuclear protein 1 (NUPR1), and selenoprotein M (SELM). Methods: TCGA-BLCA analyses were combined with silencing, overexpression, and rescue experiments in 5637 and T24 cells. Viability, migration, invasion, colony formation, glucose uptake, lactate production, extracellular acidification, oxygen consumption, and OCT4/SOX2 expression were assessed. Protein interactions and promoter-associated regulation were examined using co-immunoprecipitation, immunofluorescence, chromatin immunoprecipitation, and reporter assays. Xenograft experiments in female BALB/c nude mice evaluated NUPR1 depletion with or without SP4 overexpression. Results: Higher NUPR1 expression was associated with higher glycolysis- and stemness-associated transcriptional scores in TCGA-BLCA tumors. NUPR1 depletion reduced viability, glycolytic activity, glucose uptake, lactate production, and OCT4/SOX2 expression while increasing oxygen consumption. SP4 interacted with NUPR1 and showed enrichment at the NUPR1 promoter region. NUPR1 promoted SELM expression and reporter activity, with enrichment detected at the SELM promoter region. SP4 or SELM overexpression partially rescued the effects of NUPR1 depletion. SELM silencing attenuated NUPR1-associated increases in viability, migration, invasion, and colony formation. NUPR1 depletion suppressed xenograft growth, which was partially rescued by SP4 overexpression. Conclusions: These findings support functional relationships among SP4, NUPR1, and SELM that connect glycolytic activity with stemness-associated phenotypes in bladder cancer models. The results provide a basis for further investigation of this regulatory network in cancer metabolism.
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BibTeX
@article{deng2026sp4nupr1selm,
title = {{The SP4–NUPR1–SELM Axis Promotes Glycolytic Reprogramming and Stemness-Associated Phenotypes in Bladder Cancer}},
author = {Hannuo Deng and Rui Sun and Guangming He and Yuchen Tan and Lei Zhang and Shenglin Gao and Yichao Zhu and Lifeng Zhang and Li Zuo and Zhiqi Tang},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203396},
url = {https://www.mdpi.com/2072-6694/18/20/3396},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The SP4–NUPR1–SELM Axis Promotes Glycolytic Reprogramming and Stemness-Associated Phenotypes in Bladder Cancer
AU - Hannuo Deng
AU - Rui Sun
AU - Guangming He
AU - Yuchen Tan
AU - Lei Zhang
AU - Shenglin Gao
AU - Yichao Zhu
AU - Lifeng Zhang
AU - Li Zuo
AU - Zhiqi Tang
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18203396
UR - https://www.mdpi.com/2072-6694/18/20/3396
AB - Background: Metabolic adaptation and stemness-associated programs contribute to bladder cancer growth. This study investigated the regulatory and functional relationships among specificity protein 4 (SP4), nuclear protein 1 (NUPR1), and selenoprotein M (SELM). Methods: TCGA-BLCA analyses were combined with silencing, overexpression, and rescue experiments in 5637 and T24 cells. Viability, migration, invasion, colony formation, glucose uptake, lactate production, extracellular acidification, oxygen consumption, and OCT4/SOX2 expression were assessed. Protein interactions and promoter-associated regulation were examined using co-immunoprecipitation, immunofluorescence, chromatin immunoprecipitation, and reporter assays. Xenograft experiments in female BALB/c nude mice evaluated NUPR1 depletion with or without SP4 overexpression. Results: Higher NUPR1 expression was associated with higher glycolysis- and stemness-associated transcriptional scores in TCGA-BLCA tumors. NUPR1 depletion reduced viability, glycolytic activity, glucose uptake, lactate production, and OCT4/SOX2 expression while increasing oxygen consumption. SP4 interacted with NUPR1 and showed enrichment at the NUPR1 promoter region. NUPR1 promoted SELM expression and reporter activity, with enrichment detected at the SELM promoter region. SP4 or SELM overexpression partially rescued the effects of NUPR1 depletion. SELM silencing attenuated NUPR1-associated increases in viability, migration, invasion, and colony formation. NUPR1 depletion suppressed xenograft growth, which was partially rescued by SP4 overexpression. Conclusions: These findings support functional relationships among SP4, NUPR1, and SELM that connect glycolytic activity with stemness-associated phenotypes in bladder cancer models. The results provide a basis for further investigation of this regulatory network in cancer metabolism.
SN - 2072-6694
ER -