bims-meproc Biomed News
on Metabolism in Prostate Cancer
Issue of 2026–05–03
seventeen papers selected by
Grigor Varuzhanyan, UCLA
  1. USP13 promotes enzalutamide resistance by catalyzing depolyubiquitination of PCMT1 in prostate cancer.
  2. Fibromodulin positively regulated by Androgen Receptor, promotes prostate cancer progression via the PI3K/AKT signaling pathway and epithelial-medenchymal transition.
  3. AR-targeted therapies sensitize prostate cancer to cuproptosis by transcriptionally activating FDX1.
  4. Icaritin inhibits castration-resistant prostate cancer via RhoB-mediated Akt signaling.
  5. Elucidating the Potential Targets and Mechanisms of Bisphenol A-Induced Prostate Cancer Based on Network Toxicology and Molecular Docking Analyses.
  6. GLUL drives metabolic reprogramming and confers docetaxel resistance in prostate cancer.
  7. Prostate cancer cells' growth is decreased by novel MYC inhibitors.
  8. Metformin in prostate cancer: a context-dependent antitumour strategy driven by metabolic vulnerability and signalling network.
  9. Proteomic Profiling Reveals HECTD4-dependent Regulation of Protein Ubiquitination and Signaling Pathways in Prostate Cancer.
  10. RBM14 drives prostate cancer metastasis via stabilizing HK2 mRNA to activate glycolysis and H3K18 lactylation.
  11. Comprehensive profiling reveals Sialyl-Tn upregulation and prognostic value in prostate cancer.
  12. Rewired lipid metabolism in castration-resistant prostate cancer: molecular interplay between glucose metabolism and sterol synthesis.
  13. miR-30b-5p suppresses prostate cancer progression by targeting FLVCR1 through the cAMP/PKA/CREB pathway.
  14. Integrative multi-omics analysis identifies key ubiquitination regulators in prostate cancer.
  15. Anoctamin 5 as a protective factor in prostate cancer: Insights from WGCNA, machine learning, and experimental analysis, with a focus on the anoctamin family.
  16. ECM (collagen) mediated signaling drives the emergence of androgen independence in prostate cancer cells.
  17. Integrative Computational Approaches to Prostate Cancer with Conditional Reprogramming and AI-Driven Precision Medicine.
  1. Cell Death Dis. 2026 Apr 30.
    USP13 promotes enzalutamide resistance by catalyzing depolyubiquitination of PCMT1 in prostate cancer.
    Zhipeng Wang, Xiaoqiang Liu, Zhongqi Li, Ruize Yuan, Fuchun Zheng, Situ Xiong, Jin Zeng, Wan Pang, Bin Fu, Sheng Li, Songhui Xu, Jun Deng.
      Castrate resistant prostate cancer (CRPC) is often driven by constitutively active androgen receptor and AR splicing variants that become resistant to established hormonal therapy strategies such as enzalutamide. Deubiquitinating enzymes (DUBs) play crucial roles in cancer development, progression, and metastasis by epigenetic modification. Hence, targeting DUBs might prove to be a valid strategy for developing novel anti-cancer therapeutics. Here, we reveal that the deubiquitinating enzyme USP13 is up-regulated in PCa tissues and correlates with prostate cancer progression. USP13 silencing inhibits prostate cancer cell growth in vitro and in vivo. Mechanically, USP13 directly interacts with PCMT1 and removes polyubiquitination of PCMT1 to maintain its stability, which promotes PCa cell proliferation and enzalutamide resistance. Depletion of USP13 promoted PCa cells sensitive to enzalutamide. Clinically, USP13 was significantly up-regulated in prostate cancer tissues and positively associated with PCMT1 expression. Notably, inhibition of USP13 significantly decreases prostate tumor growth and improves enzalutamide treatments through PCMT1 suppression. Our studies demonstrate that inhibition of USP13 can offer a viable therapeutic option to overcome enzalutamide resistance in prostate cancer patients with USP13/PCMT1-overexpression.
    DOI:  https://doi.org/10.1038/s41419-026-08824-9
  2. Mol Biol Rep. 2026 Apr 25. pii: 669. [Epub ahead of print]53(1):
    Fibromodulin positively regulated by Androgen Receptor, promotes prostate cancer progression via the PI3K/AKT signaling pathway and epithelial-medenchymal transition.
    Jingzhe Fu, Danfeng Zhao, Zhenjie Zang, Xuesheng Wang, Hui Zhang, Qiang Fu.
       BACKGROUND: The progression of prostate cancer is predominantly driven by androgen receptor (AR) signaling; however, its downstream effector molecules are not fully characterized. Fibromodulin (FMOD), a proteoglycan with established roles in other cancers, has recently been implicated in prostate cancer; however, the precise molecular mechanisms underlying its regulation and oncogenic function remain elusive. Here, we sought to elucidate the functional role of FMOD and its regulation by the AR and the subsequent activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling axis.
    METHODS: FMOD expression levels across multiple prostate cancer cell lines were quantified by qRT-PCR and Western blot analysis. To investigate its function, transient knockdown using small interfering RNA (siRNA) was Performed in LNCaP and 22Rv1 cells, while lentiviral-mediated overexpression of FMOD was established in LNCap cells, to assess cellular proliferation, migration, invasion, and cell cycle distribution in vitro. For in vivo studies, a stable FMOD-knockdown model was established using lentiviral-mediated shRNA to evaluate tumor growth in xenograft mice. Putative upstream transcription factors were predicted using the JASPAR database and validated through AR knockdown experiments. Downstream signaling pathways, specifically PI3K/AKT and epithelial-mesenchymal transition (EMT), were analyzed via Western blot.
    RESULTS: FMOD was highly expressed in LNCaP and 22Rv1 cells. FMOD knockdown markedly suppressed cell proliferation, induced cell cycle arrest, and inhibited migration and invasion by reversing the EMT process. In vivo experiments confirmed that FMOD depletion significantly retarded tumor growth. Mechanistically, we identified FMOD as a transcriptional target positively regulated by AR. Furthermore, FMOD facilitated cancer progression by activating the PI3K/AKT signaling pathway.
    CONCLUSION: Our findings delineate a critical AR-FMOD-PI3K/AKT signaling axis in prostate cancer progression. FMOD serves as a key downstream effector of AR and may represent a promising therapeutic target for clinical intervention.
    Keywords:  Androgen receptor; FMOD; Prostate cancer; PI3K/AKT signaling pathway; Tumor progression
    DOI:  https://doi.org/10.1007/s11033-026-11651-y
  3. Proc Natl Acad Sci U S A. 2026 May 05. 123(18): e2534978123
    AR-targeted therapies sensitize prostate cancer to cuproptosis by transcriptionally activating FDX1.
    Xuehui Li, Siliang Wang, Yuang Wei, Chuang Xie, Yanhua Chen, Fanchen Wu, Qianqian Zhou, Xiaowen Song, Xinyi Xu, Dongliang Xu, Lingfan Xu, Shan Lin, Fuwen Yuan.
      Androgen receptor (AR) signaling is central to prostate cancer progression, yet resistance to AR-targeted therapies remains a major clinical challenge. Understanding the molecular consequences of AR pathway inhibition is therefore essential for improving therapeutic outcomes. Here, we identify a previously unrecognized link between AR antagonism and cuproptosis, a copper-dependent form of regulated cell death. Using integrated genomic profiling, we find that AR-targeted agents transcriptionally activate the key cuproptosis regulator Ferredoxin-1 (FDX1), thereby rendering prostate cancer cells markedly more susceptible to copper-induced lethality. Mechanistically, ligand-bound AR directly engages FDX1 cis-regulatory elements, which are rendered accessible by the pioneer factor GATA2, and drives FDX1 upregulation upon AR antagonist exposure. Consistent with this mechanism, FDX1 expression is elevated in clinical prostate cancer samples following androgen deprivation therapy or AR antagonist treatment. Increased FDX1 enhances intracellular Cu+ accumulation, destabilizes Fe-S cluster proteins, and disrupts mitochondrial metabolism, establishing a procuproptotic state. Functionally, combining AR antagonists with copper ionophores synergistically induces cuproptosis and potently suppresses tumor growth in AR-positive prostate cancer cells, three-dimensional (3D) spheroids, patient-derived organoids, and xenograft models, with minimal systemic toxicity. This synergy is abolished by FDX1 loss or copper chelation, confirming dependence on AR-FDX1 axis activation. Together, these findings uncover FDX1 as a mechanistic effector of AR pathway inhibition and propose a well-tolerated combination strategy that exploits cuproptosis to improve therapeutic responses in prostate cancer.
    Keywords:  FDX1; androgen receptor (AR); cuproptosis; prostate cancer
    DOI:  https://doi.org/10.1073/pnas.2534978123
  4. Pathol Res Pract. 2026 Apr 18. pii: S0344-0338(26)00129-9. [Epub ahead of print]283 156476
    Icaritin inhibits castration-resistant prostate cancer via RhoB-mediated Akt signaling.
    Chen Hui, Zhang Fan, Ma Yingyao, Gan Shu, Su Tao.
      Current therapeutic regimens for castration-resistant prostate cancer (CRPC) are plagued by multiple limitations. RhoB has emerged as a promising molecular target for prostate cancer (PCa) therapy. Icaritin, a bioactive prenylated flavonoid isolated from Epimedii Folium, exhibits potent antitumor and osteogenic properties. However, the anti-CRPC efficacy of icaritin and its underlying molecular mechanisms remain incompletely elucidated. Herein, we evaluated the anti-CRPC potential of icaritin and investigated the involvement of RhoB signaling. Results demonstrated that icaritin significantly suppressed the viability, proliferation, and clonogenic capacity of CRPC cells. Furthermore, in an RM-1 xenograft model, icaritin inhibited tumor growth and reduced serum levels of prostate-specific antigen (PSA) and testosterone. Integrated RNA-seq analysis and The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD) dataset identified RhoB as a candidate therapeutic target in CRPC. Subsequent mechanistic investigations revealed that icaritin inhibits CRPC progression by modulating RhoB-mediated Akt signaling. Collectively, these findings indicate that the anti-CRPC activity of icaritin is at least partially mediated through the RhoB/Akt signaling, providing a pharmacological basis for the further development of icaritin as a potential therapeutic agent against CRPC.
    Keywords:  AKT; Icaritin; RhoB; castration-resistant prostatic cancer
    DOI:  https://doi.org/10.1016/j.prp.2026.156476
  5. Oncol Res. 2026 ;34(5): 35
    Elucidating the Potential Targets and Mechanisms of Bisphenol A-Induced Prostate Cancer Based on Network Toxicology and Molecular Docking Analyses.
    Ashuai Du, Dianbin Guo, Dongbo Yuan, Kai Li, Yuanyuan Luo, Songsong Tan, Xuchao Dai, Bo Yu, Wanxiang You, Junjie Zhao, Bo Yan, Kehua Jiang, Xiaofei Fan, Jianguo Zhu.
       Background: Bisphenol A (BPA) is a widely used industrial chemical and endocrine-disrupting compound, and accumulating evidence suggests that it may contribute to prostate cancer progression; however, the underlying molecular mechanisms remain incompletely elucidated. This study aimed to elucidate the molecular targets and signaling pathways underlying BPA-induced prostate cancer progression.
    Methods: In this study, an integrated strategy combining network toxicology, molecular docking, and molecular dynamics simulations was employed to identify potential BPA-related targets and signaling pathways involved in prostate cancer. Candidate targets were retrieved from public databases, followed by protein-protein interaction network analysis to screen key hub genes. Functional assays were performed to evaluate the effects of BPA on prostate cancer cell migration, invasion, epithelial-mesenchymal transition (EMT), and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling, and an in vivo mouse model was used to assess the impact of BPA exposure and PI3K inhibition on tumor progression.
    Results: Eighteen BPA-related core targets were identified, among which androgen receptor (AR), matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 2 (MMP2), kallikrein-related peptidase 3 (KLK3), and hypoxia-inducible factor 1 alpha (HIF1A) emerged as key hub genes. Computational analyses indicated stable predicted interactions between BPA and these proteins. Functionally, BPA exposure promoted prostate cancer cell invasion and EMT, which were associated with activation of the PI3K/AKT and MMP signaling pathways, whereas the PI3K inhibitor LY294002 effectively attenuated BPA-induced invasive phenotypes in vitro and reduced tumor progression in vivo.
    Conclusions: Collectively, these findings provide mechanistic insights into BPA-driven prostate cancer progression and highlight the value of network toxicology-based approaches in environmental toxicology research.
    Keywords:  Bisphenol A; LY294002; network toxicology; phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling; prostate cancer
    DOI:  https://doi.org/10.32604/or.2026.076716
  6. Biochem Pharmacol. 2026 Apr 25. pii: S0006-2952(26)00341-2. [Epub ahead of print]250(Pt 2): 118008
    GLUL drives metabolic reprogramming and confers docetaxel resistance in prostate cancer.
    Zihang Wu, Yuqi Wu, Qiuxia Ding, Wei Huang, Yuanfei Huang, Ying Zhang, Ran Xu, Xiangwei Wang.
      Docetaxel is a first-line chemotherapeutic agent for advanced and castration-resistant prostate cancer (CRPC), yet acquired resistance limits its long-term efficacy. Metabolic reprogramming has emerged as a central mechanism of therapeutic resistance; however, the metabolic determinants of docetaxel resistance remain incompletely defined. Here, we identify glutamate-ammonia ligase (GLUL), the key enzyme mediating de novo glutamine synthesis, as a critical regulator of docetaxel resistance. Integrated transcriptomic, metabolomic, and single-cell RNA sequencing analyses of clinical specimens revealed significant enrichment of amino acid metabolic pathways, with glutamine metabolism as a dominant alteration. GLUL was consistently upregulated in resistant tumors and validated across independent cohorts. High GLUL expression was associated with activation of PI3K-AKT-mTOR signaling, glycolysis, and oxidative phosphorylation. Functionally, GLUL overexpression enhanced glutamine metabolic flux, promoted cell cycle progression, suppressed docetaxel-induced apoptosis, and increased cell viability under treatment. Conversely, GLUL knockdown restored chemosensitivity in resistant cells and significantly suppressed tumor growth in xenograft models. Mechanistically, GLUL-driven metabolic reprogramming reshaped bioenergetic and redox homeostasis and was tightly coupled to pro-survival signaling activation, forming a coordinated metabolism-signaling network that supports chemoresistance. Collectively, these findings establish GLUL as a key metabolic driver of docetaxel resistance and highlight glutamine synthesis as a pharmacologically actionable vulnerability in CRPC.
    Keywords:  Chemoresistance; Docetaxel; GLUL; Glutamine; Prostate cancer
    DOI:  https://doi.org/10.1016/j.bcp.2026.118008
  7. Invest New Drugs. 2026 Apr 28.
    Prostate cancer cells' growth is decreased by novel MYC inhibitors.
    Bita Nickkholgh, Joseph McGrath, Sivanandane Sittadjody, Jay Chauhan, Steven Fletcher, K C Balaji.
      The MAX (MYC-associated protein X) was discovered as an obligate heterodimer of MYC, a protein product of a prolific proto-oncogene that is dysregulated in over three-fourths of cancers. Targeting MYC directly is fraught with challenges due to the disordered structure of the MYC protein that is not conducive for small molecule inhibitor design. Therefore, the MYC/MAX protein-protein interaction provides an opportunity for indirect targeting of MYC. We compared the efficacy of first- and second-generation MYC/MAX small molecular inhibitors, 10,058-F4 and 3jc48-3 respectively, and tested the novel class of proteomimetic MYC/MAX inhibitor JKY-2-169 on inhibiting growth of human prostate cancer cell line DU145 in 2D culture. In addition, we validated the efficacy of inhibitors using 3-dimensional (3D) systems: 3D microcapsules and human prostate cancer spheroids generated by harvesting fresh cancerous tissue from human radical prostatectomy surgical specimens. Treatment in both 3D models showed that 3jc48-3 and JKY-2-169 reduced cell viability. Analysis of patient-derived spheroids before and after treatment showed that spheroid growth increased significantly over time only in the DMSO control group, while inhibitor-treated spheroids did not show significant growth during the same period; among the treatment groups, only 3jc48-3 significantly reduced spheroid size compared with the DMSO control. The results suggest that the proteomimetic and second-generation MYC inhibitors suppress cell growth at lower concentrations compared to the first-generation inhibitors. Comparative proteomic analysis of treated and untreated DU145 cells, based on a pre-defined twofold expression threshold, identified common cellular pathways altered by MYC/MAX inhibition primarily involving cytoskeletal organizations, cell cycle regulation, metabolism, and RNA-related functions. This study provides promising preliminary in vitro support for further investigation and development of novel MYC inhibitors.
    Keywords:  3D culture; DU145; MAX; MYC; Prostate cancer; Protein–protein interaction; Proteomics; Proteomimetic; Spheroids
    DOI:  https://doi.org/10.1007/s10637-026-01613-3
  8. Discov Oncol. 2026 Apr 28.
    Metformin in prostate cancer: a context-dependent antitumour strategy driven by metabolic vulnerability and signalling network.
    Lingling Yan, Dan Chen, Tong Wu, Junpeng Zhao, Xuebing Xu, Weisong Xu, Hong Zhang, Mingbing Xiao.
      Prostate cancer (PCa) is one of the most common malignant tumours in men and imposes a significant disease burden worldwide. Existing treatments have limitations such as drug resistance, and drug repurposing provides a new direction for drug management. Among the drugs explored, metformin has demonstrated certain preventive potential. Epidemiological evidence suggests that long-term use of metformin may be associated with reduced PCa incidence. This potential benefit is particularly evident in Asian and European populations. However, existing studies still exhibit heterogeneity, publication bias, and stage-specific variability. Its clinical efficacy varies by disease stage and individual patient characteristics: although it may reduce disease-specific mortality, evidence for consistent survival benefits remains limited and inconsistent. Notably, metformin possesses a favourable and controllable safety profile. Mechanistically, metformin exerts its antitumour effects through a coordinated network of metabolic and signalling pathways rather than a single dominant mechanism. In many prostate cancer contexts, inhibition of mitochondrial complex I likely represents a primary upstream event, leading to bioenergetic stress. This metabolic perturbation subsequently activates AMP-activated protein kinase (AMPK), suppresses mTOR signalling, and modulates androgen receptor (AR)-associated pathways. In parallel, metformin induces oxidative stress remodelling by increasing reactive oxygen species and disrupting redox homeostasis, which further contributes to tumour growth inhibition. Clinically, metformin does not yet show consistent survival benefits across unselected prostate cancer populations, but it may have potential value in specific disease stages and metabolically defined patient subgroups.
    Keywords:  Antitumour effects; Drug repurposing; Mechanism of action; Metformin; Prostate cancer
    DOI:  https://doi.org/10.1007/s12672-026-05097-8
  9. Cancer Genomics Proteomics. 2026 May-Jun;23(3):23(3): 430-447
    Proteomic Profiling Reveals HECTD4-dependent Regulation of Protein Ubiquitination and Signaling Pathways in Prostate Cancer.
    Yasuo Takashima, Masami Tanaka, Kengo Yoshii, Tomohito Yagi, Aya Miyagawa-Hayashino, Kei Tashiro.
       BACKGROUND/AIM: Prostate cancer (PCa) is a leading malignancy in men, and understanding its molecular mechanisms is crucial for advancing therapeutic strategies. Ubiquitination, a key post-translational modification, regulates protein degradation and signaling, playing a vital role in cancer progression. This study focuses on HECTD4, a HECT-type E3 ubiquitin ligase, to identify its ubiquitination targets and understand its role in PCa.
    MATERIALS AND METHODS: HECTD4 knockdown was performed in LNCaP, PC-3, and DU145 PCa cell lines. A combination of semi-quantitative PCR and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify proteins with altered expression and ubiquitination profiles. Gene ontology analysis, pathway analysis, and a proliferation assay were conducted to explore the biological significance of HECTD4.
    RESULTS: We identified 1,605 downregulated and 1,736 upregulated proteins upon HECTD4 knockdown. Key proteins involved in tumor suppression and cell cycle regulation, such as NUSAP1, CDK6, and MED13L, were ubiquitinated by HECTD4. Functional annotations revealed that these targets are associated with critical pathways, including phosphoinositide 3-kinase (PI3K)-AKT, Ras-mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR), as well as immune infiltration, drug response, and survival analysis.
    CONCLUSION: HECTD4 regulates protein stability and activation through ubiquitination, impacting cell cycle progression, tumor suppression, and immune response in PCa. These findings suggest that HECTD4 is a promising therapeutic target, with potential applications in drug development aimed at disrupting oncogenic signaling and enhancing treatment efficacy.
    Keywords:  HECTD4; cell type specificity; prostate cancer; proteomics; ubiquitin-proteasome
    DOI:  https://doi.org/10.21873/cgp.20583
  10. Cell Death Discov. 2026 Apr 30.
    RBM14 drives prostate cancer metastasis via stabilizing HK2 mRNA to activate glycolysis and H3K18 lactylation.
    Zhenhong Liu, Haixin Guo, Zhijiao You, Haichao Lin, Weihui Liu, Jiabi Chen, Qingliu He, Wei Zhuang.
      Metastasis is a leading cause of poor prognosis in prostate cancer (PCa), yet its underlying regulatory mechanisms remain incompletely understood. Following the establishment of highly invasive PC-3M cell lines, RBM14 expression was found to be significantly elevated in highly invasive cells. Furthermore, RBM14 was upregulated in PCa tissues and positively correlated with adverse clinicopathological features. Functional assays demonstrated that RBM14 significantly promoted PCa cell metastasis in vitro and in vivo. Mechanistically, RBM14 bound HK2 mRNA via its RRM1/2 domains to enhance HK2 stability, thereby upregulating HK2 expression. This increased HK2 level boosted PCa cells' glycolytic capacity, which in turn led to increased global lactylation, especially in histone H3 lysine 18 lactylation (H3K18la). The elevated H3K18la preferentially enriched at the promoters of metastasis-related genes, further upregulating their expression. Importantly, combining RBM14 knockdown with 2-DG exerted a synergistic inhibitory effect on PCa metastasis. Collectively, this study identifies RBM14 as a key regulator of PCa metastasis via the HK2-glycolysis-H3K18la axis, providing a potential therapeutic target for combating PCa metastasis.
    DOI:  https://doi.org/10.1038/s41420-026-03131-w
  11. bioRxiv. 2026 Apr 15. pii: 2026.04.14.718221. [Epub ahead of print]
    Comprehensive profiling reveals Sialyl-Tn upregulation and prognostic value in prostate cancer.
    Kirsty Hodgson, Libby Blencoe, Erin Smith, Aswini Sasikumar, Ziqian Peng, Margarita Orozco-Moreno, Richard Beatson, Paula A Videira, Jennifer Munkley.
      Prostate cancer is a common cancer in males and there is an urgent unmet clinical need to identify new therapies for advanced disease. Aberrant glycosylation is common in prostate cancer and plays a functional role in disease progression. The sialyl-Tn antigen (sTn) has been widely studied in cancer, yet its involvement in prostate cancer remains relatively unexplored. Here, we utilise a novel anti-sTn antibody (L2A5) to comprehensively monitor sTn expression levels in clinical prostate cancer tissues encompassing normal, benign, primary, metastatic castrate-resistant prostate cancer (CRPC), and patient-derived xenografts (PDXs). We show that while sTn is detected at low or negligible levels in normal prostate tissues, it is expressed in 44% of prostate tumours, and prostate cancer patients with high sTn levels have significantly poorer survival times. Analysis of metastatic therapy resistant prostate-derived tumours growing in liver and bone, shows sTn is expressed in 37.5% of cases. Furthermore, we show sTn is expressed in nearly half of PDXs tested, supporting the use of PDX models as tools for testing anti-sTn therapeutic strategies. These findings identify sTn as potential prognostic biomarker and therapeutic target in prostate cancer and lay the groundwork for the development of sTn-targeted precision therapies for advanced disease.
    DOI:  https://doi.org/10.64898/2026.04.14.718221
  12. Mol Biol Rep. 2026 Apr 28. pii: 689. [Epub ahead of print]53(1):
    Rewired lipid metabolism in castration-resistant prostate cancer: molecular interplay between glucose metabolism and sterol synthesis.
    Harini Priyadharshini K B, Sumathy Arockiasamy, Sriram Krishnamoorthy.
      
    Keywords:   De novo lipogenesis; Castration-resistant prostate cancer; Metabolic reprogramming; Phytochemical adjuvants
    DOI:  https://doi.org/10.1007/s11033-026-11837-4
  13. Sci Rep. 2026 Apr 27.
    miR-30b-5p suppresses prostate cancer progression by targeting FLVCR1 through the cAMP/PKA/CREB pathway.
    Dong Shi, Yurui Tang, Chong Lu, Haoran Yang, Wei He.
      
    Keywords:  FLVCR1; Progression; Prostate cancer; The cAMP/PKA/CREB pathway; miR-30b-5p
    DOI:  https://doi.org/10.1038/s41598-026-50576-1
  14. Transl Oncol. 2026 Apr 28. pii: S1936-5233(26)00125-7. [Epub ahead of print]68 102788
    Integrative multi-omics analysis identifies key ubiquitination regulators in prostate cancer.
    Hairong Wei, Chen Gong, Zhiyong Tan, Engui Yang, Yinglong Huang, Ye An, Haihao Li, Dihao Lv, Chadanfeng Yang, Wujie Chen, Haifeng Wang, Senmao Li, Mingxia Ding, Jiansong Wang.
       BACKGROUND: Ubiquitination plays a crucial role in tumor regulation, yet its specific functions in prostate cancer (PCa) remain incompletely understood. This study aimed to identify key genes associated with ubiquitination processes in PCa and validate their roles across multiple biological levels.
    METHODS: We integrated single-cell RNA sequencing (scRNA-seq) data from the GEO database with summary-level genome-wide association study (GWAS) data. Through differential expression analysis, summary data-based Mendelian randomization (SMR), and single-cell trajectory analysis, ubiquitination-related genes (URGs) associated with PCa were screened. Validation was performed at both tissue and cellular levels: immunohistochemistry (IHC) on 30 PCa tissue samples stratified by Gleason grade (low-grade: ≤ 3 + 4; high-grade: ≥ 4 + 3), and Western blot (WB) along with quantitative PCR (qPCR) on PCa cell lines (22Rv1, LNCaP, PC-3) versus a normal prostate epithelial cell line (RWPE-1). Functional experiments including Transwell migration, wound healing, CCK-8 proliferation assays, and a cell line-derived xenograft (CDX) mouse model were conducted to validate the biological function of TRIM8.
    RESULTS: T lymphocytes and epithelial cells were the predominant cell types in the PCa microenvironment. SMR and MR analyses identified POLI and TRIM8 as key causal genes with significant protective associations against PCa (POLI: OR = 0.9385, P = 0.0046; TRIM8: OR = 0.8648, P < 0.001). Colocalization analyses supported their genetic regulatory roles. Molecular docking indicated a high binding affinity between selegiline hydrochloride and POLI (ΔG = -11.3kcal/mol). Experimental validations confirmed these findings: IHC revealed elevated POLI expression in high-grade tumors and higher TRIM8 expression in low-grade tumors. Consistently, WB and qPCR analyses demonstrated that POLI was significantly upregulated, while TRIM8 was downregulated, in PCa cell lines compared to normal controls. Functional assays further demonstrated that TRIM8 overexpression suppressed PC-3 cell migration, proliferation, and in vivo tumor growth, whereas TRIM8 knockdown exerted opposite effects, confirming its tumor-suppressive role.
    CONCLUSIONS: POLI and TRIM8 are key ubiquitination regulators with causal links to PCa pathogenesis, exhibiting distinct expression patterns correlated with tumor aggressiveness. Functional validation confirms TRIM8 as a tumor suppressor in PCa. These genes represent promising therapeutic targets, and the predicted interaction with selegiline hydrochloride highlights a potential drug-repurposing strategy.
    Keywords:  Mendelian randomization; Prostate cancer; Single-cell RNA sequencing; Summary data-based mendelian randomization; Ubiquitination
    DOI:  https://doi.org/10.1016/j.tranon.2026.102788
  15. Transl Oncol. 2026 Apr 27. pii: S1936-5233(26)00120-8. [Epub ahead of print]68 102783
    Anoctamin 5 as a protective factor in prostate cancer: Insights from WGCNA, machine learning, and experimental analysis, with a focus on the anoctamin family.
    Jian-She Wang, Li-Li Shao, Dan Yao, Dong-Mei Sun, Jian-Jun Lan, Zhi-Rong Cong.
       OBJECTIVES: Prostate cancer (PCa) is a prevalent malignancy in males, triggered by multiple factors. This study aimed to identify PCa-specific key genes with clinical significance and clarify their roles in PCa progression.
    METHODS: To screen PCa-specific key genes, a comprehensive analytical strategy was adopted by integrating weighted gene co-expression network analysis (WGCNA) for mining highly correlated important genes, Cox regression analysis for evaluating clinical relevance, and multiple machine learning techniques. Functional validation experiments were further conducted, including CCK-8 assay to assess cell proliferation, transwell assay, and wound healing assay to detect cell invasion and migration abilities after ANO5 overexpression in PCa cells. In addition, a model was constructed using machine learning to systematically clarify the role of ANO family genes in the occurrence of PCa.
    RESULTS: Anoctamin 5 (ANO5) was identified as a PCa-specific key gene through the integrated analytical approach. Clinical data analysis revealed that higher ANO5 expression was significantly correlated with favorable clinical status and longer survival time of PCa patients. Functional experiments confirmed this finding: the overexpression of ANO5 in PCa cells has an inhibitory effect on the behavior of tumor cells. Transwell and wound healing experiments further confirmed that ANO5 can inhibit the migration of PCa cells.
    CONCLUSION: ANO5 is a PCa-specific key gene that correlates with favorable clinical outcomes and regulates PCa cell invasion, suggesting its potential as a prognostic biomarker and therapeutic target. In comparison, the systematic exploration of ANO family genes enriches the understanding of PCa oncogenesis mechanisms.
    Keywords:  Anoctamin 5; Anoctamin family; Biomarker; Prognostic model; Prostate cancer
    DOI:  https://doi.org/10.1016/j.tranon.2026.102783
  16. Biochem Biophys Rep. 2026 Jun;46 102580
    ECM (collagen) mediated signaling drives the emergence of androgen independence in prostate cancer cells.
    Apoorva Abikar, Prathibha Ranganathan.
      Extracellular matrix is a major structural component of the tumor microenvironment. It is a dynamic entity that undergoes continuous deposition, remodeling and degradation to maintain tissue homeostasis. ECM plays crucial roles in providing mechanical support, modulating the microenvironment as well as serves as a reservoir for signaling molecules. Tissue stiffness is primarily determined by the abundance and cross-linking of the ECM components and in turn influences the aggressiveness and drug-response of the tumors. Collagens make up a large proportion of the total ECM. These collagens, by their interaction with cell-surface molecules like integrins, can also initiate intracellular signaling cascades and influence gene expression and tumor cell behaviour. Our group has previously identified eight different collagen types to be overexpressed in prostate cancer tissues or cultured cancer-associated fibroblasts. In this study, we have investigated•The effect of collagen on prostate cancer cell proliferation, migration and chemosensitivity•The effect of collagen-initiated signaling on androgen receptor-target gene expression under androgen-deprived conditions The results presented here suggest that under androgen-deprived conditions, ECM-mediated signaling (through FAK) can regulate AR-mediated target genes and cell proliferation. This could be a potential mechanism for emergence of androgen independence in prostate cancer.
    Keywords:  Androgen receptor signaling; Collagen; Extracellular matrix; Prostate cancer; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.bbrep.2026.102580
  17. Cells. 2026 Apr 15. pii: 700. [Epub ahead of print]15(8):
    Integrative Computational Approaches to Prostate Cancer with Conditional Reprogramming and AI-Driven Precision Medicine.
    Ahmed Fadiel, Punit Malpani, Kenneth D Eichenbaum, Frederick Naftolin, Aya Hassouneh, Geralyn Chong, Kunle Odunsi.
      Prostate cancer, particularly metastatic castration-resistant prostate cancer (mCRPC), presents therapeutic challenges rooted in adaptive lineage plasticity and neuroendocrine transdifferentiation. Conventional genome-based models fail to account for the divergent clinical trajectories observed among tumors that share identical driver mutations. This limitation requires reconceptualizing cancer as a dynamic system in which tumor cells can execute context-dependent molecular programs governed by epigenetic and transcriptional network remodeling. This review critically evaluates three convergent technological pillars reshaping prostate cancer research and clinical care. First, conditional reprogramming (CR) enables the rapid generation of patient-derived models that preserve genomic fidelity, intratumoral heterogeneity, and reversible phenotypic plasticity without genetic manipulation. Second, single-cell and spatial multi-omics approaches have clarified the cellular trajectories underlying luminal-to-neuroendocrine transdifferentiation, identifying a therapeutically actionable intermediate state. They have revealed the hierarchical transcription factor network (FOXA2-NKX2-1-p300/CBP) which orchestrates chromatin remodeling during this lethal transition. Third, physics-informed machine learning and digital twin architectures aim to move beyond correlative risk prediction toward mechanistically sound forecasting of tumor evolution, treatment response, and resistance emergence. We address unresolved challenges in prospective clinical validation, spatial heterogeneity capture, regulatory pathways for functional diagnostics, and the imperative for causal, as opposed to associative, inference from perturbational datasets. The integration of these three domains through closed-loop experimental-computational feedback cycles represents a paradigm shift from reactive to anticipatory precision oncology.
    Keywords:  FOXA2–NKX2-1; conditional reprogramming; digital twins; lineage plasticity; neuroendocrine transdifferentiation; physics-informed machine learning; precision oncology; prostate cancer; single-cell multi-omics; spatial transcriptomics
    DOI:  https://doi.org/10.3390/cells15080700
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