Prostate cancer is the second most common malignancy in men in the United States. Although second-generation anti-androgens are initially effective, eventually drug resistance develops. Hyperactivation of MEK1, a central gatekeeper protein in MAPK pathway, is observed in prostate cancer. Recently, targeting MEK1 has been a fascinating area of research. Here, our data reports that mangosteen xanthones can inhibit MEK1 kinase using a cell-free biochemical assay. Among nine xanthones, γ-mangostin and α-mangostin were most potent, and the presence of an isoprenyl group at position 8 was the key structural difference that can contribute to MEK1 inhibition. Furthermore, α-mangostin dose-dependently inhibited the p-MEK1/2(Ser217/221) and downstream target p-MSK1(Thr581) in both 22Rv1 and PC3 prostate cancer cells. The molecular docking result aligned with our findings of the inhibition assay showing a strong correlation. Taken together, the results suggest that xanthones can directly target MEK1, providing a possible opportunity for their therapeutic potential in prostate cancer.

Metastatic prostate cancer (PCa), especially when it involves the bone, remains a significant clinical challenge with limited therapeutic options. Our recent research identified Myeloid Differentiation Protein-2 (MD2/LY96) as a potential biomarker associated with poor prognosis and higher metastatic potential in PCa. In this Research Perspective, we build on those findings and present new preclinical data showing that pharmacological inhibition of MD2 markedly reduces tumor growth in a PCa mouse model of bone metastasis. Analysis of patient tumor tissues demonstrated that high MD2 expression is associated not only with metastasis but also with increased infiltration of T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs), indicating a role in promoting an immunosuppressive environment. Additionally, we show that soluble MD2 (sMD2) may serve as a non-invasive biomarker of metastatic burden and help predict resistance to poly ADP-ribose polymerase (PARP) inhibitor therapy.This Research Perspective aims to consolidate mechanistic and preclinical evidence supporting MD2 as a driver of prostate cancer metastasis and to evaluate the therapeutic potential of pharmacological MD2 inhibition in a bone metastasis model.These findings support MD2 as a novel therapeutic target and identify soluble MD2 as a promising predictive and prognostic biomarker in metastatic PCa, with mechanistic links to immune evasion and inflammatory signaling.

Regulatory roles of microRNAs in signaling pathways and their biomarker potential in prostate cancer.

CBP/p300 and BRD4 synergistically drive prostate cancer progression. Here, we report the rational design, synthesis, and biological evaluation of novel PROTACs capable of simultaneously degrading CBP/p300 and BRD4. The representative compounds 10h and 29c induced robust degradation of both targets with DC50 values ranging from 8.8 pM to 10.5 nM in PC-3 prostate cancer cells, accompanied by marked downregulation of c-Myc and acetylated H3K27. Both compounds displayed potent antiproliferative activity across multiple cancer cell lines, with higher potency than NEO2734, paclitaxel (PTX), and ARV-771. In a PC-3 xenograft mouse model, compound 29c achieved dose-dependent tumor growth inhibition (TGI) of up to 81.5% at a low dose of 0.2 mg/kg, administered every other day, significantly surpassing the efficacy of NEO2734 and PTX at higher doses. Together, 29c, a highly efficient CBP/p300 and BRD4 dual-target degrader, demonstrates significant therapeutic potential in prostate cancer and warrants further development.

ObjectiveTo assess plasma levels of heat shock protein 90α (Hsp90α) and inflammatory markers, and evaluate their diagnostic potential in prostate cancer (PCa).Patients and methodsPatients were divided into two groups based on histopathological diagnosis: PCa group and benign prostatic disease group. The levels of plasma Hsp90α and inflammatory markers were compared between groups. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Bioinformatics analysis (Gene Set Enrichment Analysis, GSEA) was further performed to explore the potential Hsp90α-related signaling pathways in PCa.ResultsPlasma Hsp90α levels were significantly higher in PCa patients compared to benign prostatic disease patients (102.8 ± 89.77vs.62.57 ± 34.82 ng/mL, p < 0.001), while PLT (213 ± 58.95vs.266 ± 70.62 *109/L, p < 0.05) and platelet-to-neutrophil ratio (PNR, 62.48 ± 24.01vs.74.33 ± 25.19, p < 0.05) were significantly lower. Plasma Hsp90α levels showed strong correlations with the M stage (p < 0.001), N stage (p < 0.01) and Clinical stage (p < 0.001), PNR was negatively correlated with M stage (p < 0.01), decreasing with tumor progression. ROC curve analysis revealed moderate diagnostic value for Hsp90α (AUC = 0.661), PLT (AUC = 0.601), and PNR (AUC = 0.590). GSEA indicated that significant correlation between Hsp90 levels and protein secretion-related pathways and cell cycle regulation signaling pathways.ConclusionsIn summary, this study demonstrates the potential clinical utility of plasma Hsp90α as an auxiliary diagnostic biomarker for PCa, particularly in advanced or metastatic disease. Furthermore, we are the first to report the diagnostic and distant metastasis risk assessment potential of PNR in PCa. Notably, diagnostic models integrating Hsp90α and PNR with prostate-specific antigen (PSA) exhibited superior performance compared to PSA alone, suggesting their complementary role. Through integrated bioinformatics analyses, we have elucidated the molecular mechanisms by which Hsp90α drives PCa progression. These findings provide novel mechanistic insights into the pathophysiology of PCa and establish a foundation for developing future diagnostic strategies and targeted therapies focusing on Hsp90α or its associated pathways.

Identifying novel gene fusions is critical for cancer diagnosis and drug development. While a few advanced methods have shown the capability to detect gene fusions involving unknown partners, comprehensive detection of gene fusions, especially of those with low copy numbers, remains a challenge. Indeed, most current panel-based sequencing methods fall short in reliability and cost efficiency. Here we present a method for detecting potentially novel gene fusions using anchored random reverse primers (ARRP) during PCR-based library construction, allowing the simultaneous capture of mutations and RNA splicing variants. Furthermore, the combination with blocker displacement amplification technology enables a median of 22-fold allele enrichment for gene fusions, achieving a limit of detection ~10-fold lower than that of current technologies and resulting in an 8-fold cost reduction. Using ARRP-seq, we identify numerous novel fusions in 98 clinical tissue samples, showcasing its diagnostic potential in prostate cancer and capacity for personalized diagnostics in cervical cancer.

Rationale: Circulating hybrid cells expressing both epithelial and immune markers have emerged as indicators of dynamic tumor-immune interactions. This study aimed to characterize circulating hybrid cells co-expressing KRT18 (pan-cytokeratin) and PTPRC (CD45), termed KP_Pos, in metastatic prostate cancer (mPCa), and to assess their molecular features, tumor microenvironmental (TME) origins, and clinical relevance. Methods: Imaging mass cytometry (IMC) was used to examine spatial relationships between CK⁺ tumor and CD45⁺ immune cells in metastatic prostate tissues. Single-cell RNA sequencing (scRNA-seq) datasets from mPCa were analyzed to identify KP_Pos cells and characterize their transcriptional heterogeneity across epithelial and immune lineages. Differentially expressed genes (DEGs) between KP_Pos and other cells were used to generate predictive gene signatures. Random forest (RF) and extreme gradient boosting (XGB) models were applied to evaluate metastatic classification performance, and high-performing signatures were validated in bulk RNA-seq datasets and correlated with clinical parameters. Results: IMC revealed frequent spatial proximity between tumor and immune compartments, supporting a TME-derived hybrid phenotype. KP_Pos cells were detected across multiple immune and epithelial clusters, showing heterogeneity and enrichment of immune response and epithelial-mesenchymal transition (EMT)-related genes. Machine learning-based classifiers using KP_Pos-derived DEGs achieved high predictive accuracy (AUC ≥ 0.7) for metastasis, and selected combinations further improved performance in internal validation sets. Signature scores significantly correlated with PSA and Gleason grade, and CD45⁺ hybrid circulating cells were more abundant in patients with advanced disease burden. Conclusions: CD45⁺ KRT18⁺ hybrid circulating cells (KP_Pos) represent biologically distinct populations shaped by tumor-immune interactions within the TME. Their transcriptomic features and derived gene signatures may serve as biomarkers of metastatic potential and indicators of disease progression in prostate cancer. However, their causal role in metastasis and impact on survival remain to be determined.

Smooth muscle (SM) invasion represents a critical feature of prostate cancer (PCa) progression and metastasis. This study aimed to develop a SM-based molecular score for progression and metastasis forecasting for PCa. A total of 952 patients with PCa with transcriptomic sequencing data and corresponding clinical information were included in this study to develop and validate a SM-related signature (SM score). SM-related molecular subtypes were identified on the basis of 35 smooth muscle-related gene sets using unsupervised clustering. Weighted gene coexpression network analysis (WGCNA) was employed to identify key SM-related genes. The SM score was subsequently developed using machine learning across, The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) training cohort and four independent external validation cohorts. Utilizing 35 gene sets related to SM function, we identified pronounced SM disruption in PCa compared with normal prostate tissues. Unsupervised consensus clustering stratified patients into two distinct molecular subtypes, which exhibited significant differences in prognosis and immune infiltration profiles. We subsequently developed a robust prognostic signature termed SM score, and multiomics analyses confirmed a strong association between the SM score and SM disruption. The SM score consistently demonstrated superior prognostic performance across all cohorts and showed potential as a biomarker for responsiveness to immunotherapy. Notably, SM score was significantly elevated in metastatic lesions compared with primary tumors and normal tissues and accurately predicted metastatic potential. SM disruption is associated with tumor progression in PCa. The SM score captures SM disruption and predicts PCa progression and metastasis potential, aiding personalized immunotherapy decisions.

The secreted phospholipase A2 human group IIA (hGIIA) is overexpressed in prostate cancer (PCa), where its expression is closely aligned with malignancy. While its enzymatic activity is important in mediating innate immunity, here we highlight that hGIIA contributes to PCa pathology primarily through specific protein-protein interactions. We have developed cyclic peptides cF and c2, derived from the structure of hGIIA, that selectively inhibit these interactions and inhibit PCa growth. hGIIA interacts directly with epidermal growth factor receptor (EGFR), resulting in increased cytosolic PLA2-α activation and prostaglandin E2 production, which is suppressed by c2. Further, vimentin was identified to bind hGIIA in PCa cells, modulating hGIIA intracellular trafficking. c2 binds vimentin, blocking this interaction and initiating vimentin-mediated aggresome formation and apoptosis even in the absence of hGIIA. cF and c2 suppress androgen-sensitive, castrate-resistant and androgen-independent models of tumour growth in vivo at doses as low as 0.1 mg/kg, are non-toxic, orally bioavailable and cell-permeable. Critically, as with hGIIA, EGFR and vimentin are also increasingly expressed as PCa develops, cF and c2 may represent a novel therapeutic option for incurable metastatic castrate resistant PCa. Our findings identify hGIIA as an innate immune effector that regulates both inflammation and PCa progression and describe a novel class of hGIIA protein-protein interaction inhibitor with therapeutic potential in PCa.

Abstract Description Objectives 1) Evaluate the therapeutic potential of the spermine-binding peptide vaccine (p25 99-118) in modulating tumor progression in a 3D MyC-CaP prostate tumor model. 2) Investigate the immune response induced by p25 99-118, focusing on CD4+ and CD8+ T cell infiltration. Methods FVB mice were immunized intraperitoneally with p25 99-118 emulsified in complete Freund’s adjuvant. Post-immunization, splenocytes were harvested and co-cultured with MyC-CaP spheroids in 3D scaffolding matrix plates. Dose-dependent effects were evaluated by adding increasing concentrations of p25 99-118, with OVA 323–339 serving as a negative control. Fixed spheroids were stained with fluorophore-conjugated anti-CD4 and anti-CD8 for confocal microscopy and then T cell infiltration quantified. Results The p25 99-118 vaccine significantly inhibited spheroid growth. Treated spheroids showed robust CD4+ and CD8+ T cell infiltration, while controls exposed to OVA 323–339 exhibited minimal infiltration, confirming antigen specificity. Conclusions The p25 99-118 vaccine induces a T cell-mediated immune response, significantly reducing tumor growth in a 3D model and highlighting its therapeutic potential in prostate cancer. Topic Categories Vaccines and Immunotherapy (VAC)

N7-methylguanosine (m7G) represents a critical posttranscriptional modification linked to oncogenesis, but its involvement in prostate cancer (PCa) remains unclear. This study focuses on WD repeat domain 4 (WDR4) and methyltransferase like 1 (METTL1) to explore their function and therapeutic potential in PCa. Using qRT-PCR, Western blot, m7G RNA immunoprecipitation (MeRIP), and functional assays (CCK-8, Transwell, TUNEL), we investigated how METTL1/WDR4 regulate m7G modification, the PI3K/AKT/mTOR cascade, and target genes (MYC and VEGF), as well as their impact on DU145 cell growth, motility, invasion, and apoptosis. Both METTL1 and WDR4 were highly expressed in PCa samples and DU145 cells, correlated with elevated m7G tRNA modification levels. Their knockdown markedly inhibited DU145 cell growth, motility, and invasion, and facilitated apoptosis. These effects were associated with reduced m7G modification, suppression of the PI3K/AKT/mTOR pathway, and downregulation of MYC and VEGF expression, showing synergistic inhibitory effects. This study reveals that METTL1 and WDR4 are overexpressed in PCa and that, in DU145 cells, their knockdown was associated with suppressed m7G modification and attenuated oncogenic phenotypes. These model-specific findings suggest that METTL1/WDR4 may represent potential therapeutic targets in prostate cancer.

Background/AimProstate cancer is the second most common malignancy among men worldwide, with progression to castration-resistant prostate cancer (CRPC) posing significant therapeutic challenges. Enzalutamide, a second-generation androgen receptor antagonist, initially demonstrates efficacy in treating metastatic CRPC; however, resistance inevitably develops. Dysregulation of the epidermal growth factor receptor (EGFR) signaling pathway has been implicated in therapy resistance and metastatic progression. Secretory carrier membrane protein 3 (SCAMP3) and epidermal growth factor receptor substrate 8 (EPS8) are known regulators of EGFR trafficking and signaling. This study aimed to investigate their cooperative roles in enzalutamide-resistant prostate cancer cells.Materials and MethodsLNCap prostate cancer cells and their enzalutamide-resistant derivatives (LNCap-Enz) were treated with 100 ng/ml epidermal growth factor (EGF). Protein expression and interactions were analyzed by Western blotting and co-immunoprecipitation. SCAMP3 and EPS8 were knocked down using shRNA technology, while complementary overexpression studies were conducted using pcDNA-SCAMP3 and pcDNA-EPS8 vectors. Effects on EGF receptor (EGFR) expression and downstream signaling molecules (STAT3, AKT, ERK) were evaluated in both loss-of-function and gain-of-function models.ResultsEGF stimulation enhanced the expression of EGFR, SCAMP3, and EPS8 in both LNCap and LNCap-Enz cells while promoting formation of a protein complex involving these proteins and the androgen receptor (AR-V7). Knockdown of SCAMP3 or EPS8 reduced EGFR expression and attenuated STAT3, AKT, and ERK activation. Conversely, overexpression of SCAMP3 or EPS8 increased EGFR levels and enhanced downstream signaling activation. These bidirectional effects highlight the functional interdependence between SCAMP3 and EPS8 in regulating EGFR stability and signaling.ConclusionSCAMP3 and EPS8 cooperatively maintain EGFR stability and signaling in prostate cancer cells, playing a critical role in enzalutamide resistance and metastatic progression. Targeting the SCAMP3-EPS8-EGFR axis offers promising therapeutic opportunities for advanced prostate cancer.

F-box and leucine-rich repeat protein 22 (FBXL22) has been implicated in breast and prostate cancer types; however, comprehensive pan-cancer analyses and detailed investigations of its role in cancer development are still needed. To address this, the present study used The Cancer Genome Atlas, Genotype-Tissue Expression, University of ALabama at Birmingham CANcer data analysis Portal, Kaplan-Meier-Plotter and cBioPortal databases to analyze the correlation between FBXL22 expression and prognosis, gene mutations, DNA methylation, immune cell infiltration and immune-related gene regulation in several types of cancer. The findings of the present study demonstrated that FBXL22 was predominantly downregulated in several cancer types and may serve as a prognostic and diagnostic marker in certain cancer types, particularly prostate cancer. Strong correlations between FBXL22 expression and immune checkpoint genes were observed, which suggests a role in the tumor immune microenvironment. Additionally, FBXL22 expression was associated with infiltration of cancer-associated fibroblasts and endothelial cells, which may affect immunotherapy outcomes. Mechanistically, FBXL22 was involved in circadian rhythm regulation, ubiquitin-mediated proteolysis, focal adhesion signaling and cGMP-protein kinase G signaling. In prostate cancer, FBXL22 upregulation suppressed cell viability, invasion and metastasis, while promoting apoptosis, potentially through modulation of the polo-like kinase 1 pathway. To the best of our knowledge, the present study provides the first comprehensive pan-cancer analysis of FBXL22, which highlights its potential as an immune biomarker and therapeutic target for multiple cancer types with implications for precision medicine.

Polybromo-1 (PBRM1) is a key subunit of the PBAF chromatin remodeling complex, linking histone lysine acetylation to transcriptional regulation through six tandem bromodomains. Targeting PBRM1 bromodomains offers therapeutic potential in prostate cancer and clear cell renal cell carcinoma. Most existing PBRM1 inhibitors also bind the structurally related SMARCA2/4 bromodomains and lack target selectivity. We and others recently developed selective PBRM1 bromodomain inhibitors that do not bind the SMARCA2/4 bromodomains. However, the key residues and binding interactions leading to selectivity for PBRM1 were unknown. Here, we solved an X-ray crystal structure of PBRM1-BD2 bound to our selective PBRM1 bromodomain inhibitor (PB16). Through mutagenesis, we identify a unique tyrosine residue in PBRM1 that creates a distinct binding pocket essential for selective inhibitor binding. Unlike GNE-235, another selective PBRM1 bromodomain inhibitor, PB16 demonstrates cell activity in PBRM1-dependent cancer models, making it a promising lead candidate to further develop for targeted cancer therapy.

Prostate cancer, a malignant tumor arising from the prostate gland, ranks as one of the most commonly diagnosed cancers in men globally and the eighth leading cause of cancer-related mortality worldwide. Hydroxamic acid derivatives, identified as outstanding histone deacetylase (HDAC) inhibitors, are a class of compounds with significant research interest in prostate cancer due to their diverse mechanisms of action, primarily involving epigenetic regulation and targeted enzyme inhibition. Recent studies highlight that incorporating diverse anti-prostate cancer pharmacophores with a hydroxamic acid moiety can potentiate their inhibitory efficacy against HDACs or endow them with multi-target HDAC inhibitory capabilities. Furthermore, hydroxamic acid hybrids possess inherent potential to enhance therapeutic efficacy through multi-target engagement, circumvent drug resistance via epigenetic reprogramming, improve pharmacokinetic profiles through structural optimization, and mitigate off-target toxicity through enhanced receptor selectivity, representing promising scaffolds for designing novel therapeutic candidates against prostate cancer. This review comprehensively outlines the research landscape of hydroxamic acid hybrids with therapeutic potential in prostate cancer, spanning from 2016 to the present, to uncover new avenues for discovering novel therapeutic candidates.

Prostate cancer (PCa) is a leading malignancy among men and lacks effective treatment, particularly for metastatic stages. Metastasis contributes significantly to cancer morbidity and mortality. Gilteritinib showed anticancer activity against lung and colorectal cancer but has not been thoroughly investigated for its potential in PCa therapy. This study evaluated the anticancer effects of gilteritinib on PCa cell lines (PC3 and DU145) by assessing cytotoxicity, cell proliferation, colony formation, and migration. Mechanistic studies were conducted to determine its impact on the cell cycle, epithelial-to-mesenchymal transition (EMT), and Wnt/β-catenin signaling. Additionally, the mode of cell death was explored, focusing on endoplasmic reticulum (ER) stress and protein ubiquitination. Gilteritinib exhibited dose-dependent cytotoxicity and inhibited PCa cell proliferation, colony formation, and migration. It induced G1 phase cell cycle arrest by downregulating CDK2, CDK4, and cyclin E1. EMT modulation was observed through the suppression of vimentin, N-cadherin, and Twist, along with increased E-cadherin expression. This EMT inhibition correlated with the downregulation of Wnt/β-catenin signaling components. Notably, gilteritinib triggered a non-apoptotic, non-autophagic cell death characterized by cytoplasmic vacuolation, ER stress, and protein ubiquitination, requiring new protein synthesis. This effect was mediated through the activation of the unfolded protein response (UPR) via the PERK pathway. Gilteritinib demonstrates significant anticancer potential in PCa by inducing cell cycle arrest, inhibiting EMT, suppressing Wnt/β-catenin signaling, and triggering a unique mode of cell death via ER stress. These findings highlight gilteritinib as a promising therapeutic candidate for PCa treatment.

Bacteria such as Vibrio spp. in the marine environment can produce secondary metabolites which have significant potential applications in pharmaceuticals. In a study to discover bioactive secondary metabolites from marine Vibrio spp., the strain DJA11 was encountered. HPLC/UV-guided isolation of the crude extract from this strain has led to the discovery of compound 1. Prostate cancer (PCa) is one of the biggest worldwide health issues because of its high diagnosis. CWR22Rv1 (22Rv1) is mutated in WT p53 and AR, C4-2 is derived from androgen-dependent human LNCaP and PC-3 is an androgen-independent cancer cell type. It was found that compound 1 exhibited no significant cytotoxicity at concentrations below 50 μM to human PCa cells, including 22Rv1, C4-2, and PC-3, like normal cell HEK293T. In addition, we presented that 1 inhibited the invasiveness and proliferation of 22Rv1, PC-3, and C4-2 cells by suppressing the activation of p-AKT, p-mTOR, p-STAT3, HSP90, and HSP70. Moreover, treatment with 1 decreased the mRNA expression level of ErbB4, PDK1, STAT3, HSP70, and HSP90 in some PCa cells. Therefore, compound 1 may have therapeutic potential in PCa due to its role in suppressing cancer proliferation and metastasis.

EDNRB negatively regulates glycolysis to exhibit anti-tumor functions in prostate cancer by cGMP/PKG pathway.

Ferroptosis inducers have shown therapeutic potential in prostate cancer, but tumor heterogeneity poses a barrier to their efficacy. Distinguishing the regulators orchestrating metabolic cross-talk between cancer cells could shed light on therapeutic strategies to more robustly activate ferroptosis. In this study, we found that aberrant accumulation of Jumonji domain-containing 6 (JMJD6) proteins correlated with poorer prognosis of patients with prostate cancer. Mechanistically, prostate cancer-associated speckle-type BTB/POZ protein (SPOP) mutants impaired the proteasomal degradation of JMJD6 proteins. Elevated JMJD6 and ATF4 coordinated enhancer-promoter loop interactions to stimulate the glutathione biosynthesis pathway. Independent of androgen receptor, JMJD6 recruited mediator subunits (Med1/14) to assemble de novo enhancers mapping to pivotal genes associated with glutathione metabolism, including SLC7A11, GCLM, ME1, and others. SPOP mutations thus induced intrinsic resistance to ferroptosis, dependent on enhanced JMJD6-ATF4 activity. Consequently, targeting JMJD6 rendered SPOP-mutated prostate cancer selectively sensitive to ferroptosis. The JMJD6 antagonist SKLB325 synergized with erastin in multiple preclinical prostate cancer models. Together, this study identifies JMJD6 as a druggable vulnerability in SPOP-mutated prostate cancer to increase sensitivity to ferroptosis inducers. Significance: Elevated JMJD6 induced by mutant SPOP alters the epigenetic landscape to increase glutathione biosynthesis and protect prostate cancer cells from ferroptosis, highlighting the therapeutic potential of combining JMJD6 inhibitors and ferroptosis inducers.

This study investigated tempol action on genes and miRNAs related to NFκB pathway in androgen dependent or independent cell lines and in TRAMP model in the early and late-stages of cancer progression. A bioinformatic search was conducted to select the miRNAs to be measured based on the genes of interest from NFκB pathway. The miR-let-7c-5p, miR-26a-5p and miR-155-5p and five target genes (BCL2, BCL2L1, RELA, TNF, PTGS2) were chosen for RT-PCR and gene enrichment analyses. In vitro, PC-3 and LNCaP cells were exposed, respectively, to 1.0 or 2.0 mM of tempol during 48h. In vivo, five experimental groups were evaluated regarding tempol effects in the early (CT12 and TPL12 groups) and late-stages (CT20, TPL20-I and TLP20-II) of PCa development. TPL groups were treated with 50mg/kg or 100mg/kg of tempol. The ventral lobe of the prostate and the plasma was collected. Tempol treatment increased miRs expression in PC-3 and LNCaP. For both cell lines, tempol decreased RELA expression. In TRAMP model, tempol increased miRNA expression in prostate for all treated groups. Tempol upregulated the miRNA expressions related to the NFκB pathway in the prostate tissue and human tumor cell lines. Their increase is mainly linked to increased cell death and delayed CaP aggressivenes. Thus, tempol's capacity for miRNA-mediated gene silencing to decrease tissue proliferation and cell survival processes is part of its tissue mechanics.