Abstract Therapy-induced neuroendocrine prostate cancer (t-NEPC) represents a subset of lethal prostate cancer (PCa) resistant to androgen deprivation therapy (ADT). Current intervention strategies for t-NEPC are largely undefined, underscoring the urgent need to better understand its molecular mechanisms. Lysine (K)-specific demethylase 5B (KDM5B), a key epigenetic regulator, is frequently elevated in advanced PCa and t-NEPC. Similarly, the transcription factor sex-determining region Y (SRY)-box 9 (SOX9) is a critical regulator of prostate development and has been implicated in PCa. In this study, we investigated the functional role of the KDM5B/SOX9 signaling pathway on the development and progression of t-NEPC. We found that the levels of KDM5B and SOX9 are abnormally elevated in human NEPC cells. Remarkably, KDM5B depletion led to a significant reduction in mRNA and protein levels of SOX9 and neuroendocrine markers (Neuron-specific enolase and Synaptophysin) in PC3 cells. Conversely, KDM5B add-back to KDM5B knockout (KO) cells restored their levels in a dose-dependent manner. Importantly, the recurrent tumors of castrated Pten/Trp53 mice displayed the malignant features of t-NEPC, along with elevated Kdm5b and Sox9 levels. Surprisingly, Kdm5b deficiency abrogated the t-NEPC progression in Pten/Trp53/Kdm5b mutant mice, indicating the essential role of Kdm5b in t-NEPC progression in vivo. Furthermore, we observed an increase in KDM5B and SOX9 levels in LNCaP-MDV cells, a LNCaP-derived NEPC cell line. Mechanistically, KDM5B regulated SOX9 signaling in PCa cells by directly binding to the SOX9 promoter. To further elucidate the contributions of the KDM5B/SOX9 signaling axis to t-NEPC progression, we generated SOX9 KO PCa cells using CRISPR/Cas9 technology. Our results showed that SOX9 KO significantly decreased the proliferation and the levels of neuroendocrine markers in PCa cells, without impacting KDM5B levels. In conclusion, our findings in vitro and in vivo demonstrate the essential role of KDM5B/SOX9 signaling pathway in the development and progression of t-NEPC, suggesting that targeting this pathway could represent a novel and effective therapeutic strategy for controlling t-NEPC. Citation Format: Guoliang Li, Sherly Celada, Qingguo Wang, Renjie Jin, Thanigaivelan Kanagasabai, Qiujia Shao, Bindong Liu, Samuel Evans Adunyah, Paula Hurley, Zhenbang Chen. The essential role of KDM5B/SOX9 signaling Axis in the development and progression of therapy-induced neuroendocrine prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1357.

Tumor-associated macrophages (TAMs) are the most abundant immune cells in primary solid tumors, including breast cancer, and typically exhibit an M2-like, immunosuppressive phenotype that promotes tumor growth. Given that TAMs can be repolarized through cytokine signaling, we propose a localized cytokine delivery depot using an injectable alginate cryogel to reprogram TAMs and create an inflammatory, anti-tumor TME. The cryogels were fabricated using cryogelation to generate a macroporous structure, followed by ionic crosslinking to enhance mechanical integrity while preserving pore size distribution. In vitro studies were conducted using bone marrow-derived macrophages, tumor-associated macrophages, and tumor explants. In vivo studies were conducted by orthotopically implanting breast tumors in the fat pads of FVB mice. Cell makeup and tissue composition were analyzed using qRT-PCR, flow cytometry, and Luminex panels. Statistical significance was determined using ANOVA and t-tests. In vitro, cryogels released chemokines and cytokines, attracted M2 macrophages, and repolarized them toward M1-like activities. In vivo, cryogel treatment increased the presence of M1 macrophages relative to M2 macrophages in both the primary tumor and lungs, reduced primary tumor growth, and decreased T-cell exhaustion. A localized, injectable cryogel depot successfully induces an inflammatory TME, leading to reduced tumor burden and T-cell exhaustion while avoiding systemic toxicities associated with cytokine delivery.

The Internet of Things (IoT) is gaining popularity as it can effectively connect the real world with the Internet. However, security and privacy issues are widely considered the major obstructions to its widespread adoption. Hence, various cryptographic tools (e.g., encryption and signature schemes) have been proposed to build secure and authenticated channels for data communication in IoT. In this work, we investigate the well-known encryption scheme called identity-based encryption (IBE) for IoT-oriented applications. In particular, we are mainly interested in forward-secure IBE (fs-IBE) which could still protect the data transferred in the past when the current secret key stored in the IoT device is stolen. To this end, we propose an fs-IBE scheme which, as far as we know, is the first construction of fs-IBE that can resist quantum attacks. Our scheme is based on the lattice-based hardness assumption namely Learning with Error (LWE), which is widely adopted for designing other quantum-resistant cryptographic schemes. At the core of our design is the minimal cover mechanism in the context of binary tree and we rigorously prove the security of our scheme in the forward-secure, selective ID, chosen-plaintext attack (CPA) model. Besides the post-quantum security, our scheme enjoys comparatively compact ciphertext and secret key, and thus it is suitable for bandwidth-limited IoT communication.

BACKGROUND:The medical therapy of prostatic symptoms (MTOPS) trial randomized men with symptoms of benign prostatic hyperplasia (BPH) and followed response of treatment with a 5α-reductase inhibitor (5ARI), an alpha-adrenergic receptor antagonist (α-blocker), the combination of 5ARI and α-blocker or no medical therapy (none). Medical therapy reduced risk of clinical progression by 66% but the reasons for nonresponse or loss of therapeutic response in some patients remains unresolved. Our previous work showed that prostatic glucocorticoid levels are increased in 5ARI-treated patients and that glucocorticoids can increased branching of prostate epithelia in vitro. To understand the transcriptomic changes associated with 5ARI treatment, we performed bulk RNA sequencing of BPH and control samples from patients who received 5ARI versus those that did not. Deconvolution analysis was performed to estimate cellular composition. Bulk RNA sequencing was also performed on control versus glucocorticoid-treated prostate epithelia in 3D culture to determine underlying transcriptomic changes associated with branching morphogenesis. METHOD:Surgical BPH (S-BPH) tissue was defined as benign prostatic tissue collected from the transition zone (TZ) of patients who failed medical therapy while control tissue termed Incidental BPH (I-BPH) was obtained from the TZ of men undergoing radical prostatectomy for low-volume/grade prostatic adenocarcinoma confined to the peripheral zone. S-BPH patients were divided into four subgroups: men on no medical therapy (none: n = 7), α-blocker alone (n = 10), 5ARI alone (n = 6) or combination therapy (α-blocker and 5ARI: n = 7). Control I-BPH tissue was from men on no medical therapy (none: n = 8) or on α-blocker (n = 6). A human prostatic cell line in 3D culture that buds and branches was used to identify genes involved in early prostatic growth. Snap-frozen prostatic tissue taken at the time of surgery and 3D organoids were used for RNA-seq analysis. Bulk RNAseq data were deconvoluted using CIBERSORTx. Differentially expressed genes (DEG) that were statistically significant among S-BPH, I-BPH, and during budding and branching of organoids were used for pathway analysis. RESULTS:Transcriptomic analysis between S-BPH (n = 30) and I-BPH (n = 14) using a twofold cutoff (p < 0.05) identified 377 DEG (termed BPH377) and a cutoff < 0.05 identified 3377 DEG (termed BPH3377). Within the S-BPH, the subgroups none and α-blocker were compared to patients on 5ARI to reveal 361 DEG (termed 5ARI361) that were significantly changed. Deconvolution analysis of bulk RNA seq data with a human prostate single cell data set demonstrated increased levels of mast cells, NK cells, interstitial fibroblasts, and prostate luminal cells in S-BPH versus I-BPH. Glucocorticoid (GC)-induced budding and branching of benign prostatic cells in 3D culture was compared to control organoids to identify early events in prostatic morphogenesis. GC induced 369 DEG (termed GC359) in 3D culture. STRING analysis divided the large datasets into 20-80 genes centered around a hub. In general, biological processes induced in BPH supported growth and differentiation such as chromatin modification and DNA repair, transcription, cytoskeleton, mitochondrial electron transport, ubiquitination, protein folding, and cholesterol synthesis. Identified signaling pathways were pooled to create a list of DEG that fell into seven hubs/clusters. The hub gene centrality was used to name the network including AP-1, interleukin (IL)-6, NOTCH1 and NOTCH3, NEO1, IL-13, and HDAC/KDM. All hubs showed connections to inflammation, chromatin structure, and development. The same approach was applied to 5ARI361 giving multiple networks, but the EGF and sonic hedgehog (SHH) hub was of particular interest as a developmental pathway. The BPH3377, 5ARI363, and GC359 lists were compared and 67 significantly changed DEG were identified. Common genes to the 3D culture included an IL-6 hub that connected to genes identified in BPH hubs that defined AP1, IL-6, NOTCH, NEO1, IL-13, and HDAC/KDM. CONCLUSIONS:Reduction analysis of BPH and 3D organoid culture uncovered networks previously identified in prostatic development as being reinitiated in BPH. Identification of these pathways provides insight into the failure of medical therapy for BPH and new therapeutic targets for BPH/LUTS.

Supplementary Figure 1 from The Nuclear Factor-κB Pathway Controls the Progression of Prostate Cancer to Androgen-Independent Growth

Supplementary Materials and Methods

Cancer Outlier Profile Analysis (COPA) in Oncomine 4.4 showing TBX2 over-expression in PCa microarray data sets

PDF file - 453KB, Supplementary Figure 1. NF-kappaB signaling is continuously activated in the prostate of IkappaBalpha+/- mouse. Supplementary Figure 2. NF-kappaB signaling activated in the prostate of Myc/IkappaBalpha bigenic mouse. Supplementary Figure 3. Continuous activation of NF-kappaB signaling promotes PCa progression in the Hi-Myc transgenic mouse. Supplementary Figure 4. The NF24 gene signature predicts significant differences in the overall cancer-specific survival of the PCa patients. Supplemental Figure 5. Molecular network analysis using Ingenuity Pathway Analysis (IPA). Supplemental Figure 6. NF-kappaB signaling is activated/inactivated in PCa cells by infecting with IKK2-EE or IKK2-KD retroviral vectors. Supplemental Figure 7. Activation of NF-kappaB signaling increases JNK phosphorylation in PCa cells. Supplemental Figure 8. Blocking JNK signaling inhibits NF-kappaB induced invasive ability efficiently in PCa cells. Tables 1 and 2. Matched human homolog genes. Supplementary Table 3. Stratification of 77 PCa patients.

<p>Micro-CT images of mouse tibiae injected with ARCaPM-TBX2 and ARCaPM-Neo cells</p>

<p>Invasion assay of PC3 (TBX2DN+WNT3A, TBX2DN, and Neo)cells with the addition of SFRP-2</p>

Legend to Supplementary Figures

<p>Schematic depiction of WNT3A gene promoter, and ChIP analysis of LNCaP-TBX2 and LNCaP-Neo cells to assess the binding of TBX2 on WNT3A promoter</p>

Quantitative Real-Time RT-PCR and Invasion assay of LNCaP-TBX2 and LNCaP-Neo cells

<p>Invasion assay of PC3 (TBX2DN+WNT3A, TBX2DN, and Neo)cells with the addition of SFRP-2</p>

<p>Plot showing relative protein expression of TBX2 and WNT3A in human PCa cell lines</p>

The development of benign prostatic hyperplasia (BPH) and medication‐refractory lower urinary tract symptoms (LUTS) remain poorly understood. This study attempted to characterize the pathways associated with failure of medical therapy for BPH/LUTS.

Sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor in lipogenesis and lipid metabolism, is critical for disease progression and associated with poor outcomes in prostate cancer (PCa) patients. However, the mechanism of SREBP-1 regulation in PCa remains elusive. Here, we report that SREBP-1 is transcriptionally regulated by microRNA-21 (miR-21) in vitro in cultured cells and in vivo in mouse models. We observed aberrant upregulation of SREBP-1, fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC) in Pten/Trp53 double-null mouse embryonic fibroblasts (MEFs) and Pten/Trp53 double-null mutant mice. Strikingly, miR-21 loss significantly reduced cell proliferation and suppressed the prostate tumorigenesis of Pten/Trp53 mutant mice. Mechanistically, miR-21 inactivation decreased the levels of SREBP-1, FASN, and ACC in human PCa cells through downregulation of insulin receptor substrate 1 (IRS1)-mediated transcription and induction of cellular senescence. Conversely, miR-21 overexpression increased cell proliferation and migration; as well as the levels of IRS1, SREBP-1, FASN, and ACC in human PCa cells. Our findings reveal that miR-21 promotes PCa progression by activating the IRS1/SREBP-1 axis, and targeting miR-21/SREBP-1 signaling pathway can be a novel strategy for controlling PCa malignancy.

The construction of quantum maximum distance separable (MDS for short) codes is one of the hot issues in quantum information theory. As far as we know, researchers have done a lot of constructive work in the construction of quantum MDS codes. However, the known results do not cover all parameters. In this paper, we propose an efficient construction implemented by concatenating two existing quantum MDS codes. Compared to a previous work (Fang and Luo in Quantum Inf Process 19(1):16, 2020), we relax the restrictions of the construction and propose some new quantum MDS codes.

The present studies were conducted to evaluate key serum proteins and other components that mediate anchorage-independent growth (3-D growth) of LNCaP prostate cancer cells as spheroids. The cells were cultured on ultra-low attachment plates in the absence and presence of fetuin-A and with or without extracellular vesicles. The data show that fetuin-A (alpha 2HS glycoprotein) is the serum protein that mediates 3-D growth in these cells. It does so by sequestering extracellular vesicles of various sizes on the surfaces of rounded cells that grow as spheroids. These vesicles in turn transmit growth signals such as the activation of AKT and MAP kinases in a pattern that differs from the activation of these key growth signaling pathways in adherent and spread cells growing in 2-D. In the process of orchestrating the movement and disposition of extracellular vesicles on these cells, fetuin-A is readily internalized in adhered and spread cells but remains on the surfaces of non-adherent cells. Taken together, our studies suggest the presence of distinct signaling domains or scaffolding platforms on the surfaces of prostate tumor cells growing in 3-D compared to 2-D.

Galois hulls of linear codes have important applications in quantum coding theory. In this paper, we construct some new classes of (extended) generalized Reed-Solomon (GRS) codes with Galois hulls of arbitrary dimensions. We also propose a general method on constructing GRS codes with Galois hulls of arbitrary dimensions from special Euclidean orthogonal GRS codes. Finally, we construct several new families of entanglement-assisted quantum error-correcting codes (EAQECCs) and MDS EAQECCs by utilizing the above results.