Molecular Biology Reports最新文献

{"title":"Targeting NMDAR2A in microglia: esketamine suppresses M1 polarization in BV2 cells.","authors":"Hui Li, Xiaoyuan Zhang, Yushan Luo, Wen Hu, Yang Liu, Yimin Ren, Xiaohua Zou","doi":"10.1007/s11033-026-12874-9","DOIUrl":"10.1007/s11033-026-12874-9","url":null,"abstract":"<p><strong>Objective: </strong>Microglial polarization toward the M1 phenotype is a key contributor to the initiation and progression of neuroinflammatory diseases, primarily through the release of pro-inflammatory cytokines that exacerbate central nervous system-associated injury. Activation of N-methyl-D-aspartic acid receptors (NMDARs) is implicated in microglial overactivation and cytotoxicity. This study aimed to investigate the role of esketamine, a non-competitive NMDAR antagonist, on microglial polarization.</p><p><strong>Methods: </strong>BV2 microglial cells were used as an in vitro model. Inhibitors and agonists were applied to modulate the mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor (BDNF)-tyrosine kinase receptor B (TrkB) signaling pathways. Small interfering RNA, Western blotting, enzyme-linked immunosorbent assay, and immunofluorescence staining were performed to investigate the regulatory effects and molecular targets of esketamine on BV2 cells.</p><p><strong>Results: </strong>Esketamine enhanced mTOR phosphorylation and activated the BDNF-TrkB signaling pathway through NMDAR inhibition. This effect attenuated lipopolysaccharide-induced M1 polarization in BV2 microglia and reduced pro-inflammatory cytokine expression. Further analysis revealed that the anti-inflammatory effects of esketamine were primarily mediated by the NMDAR2A subtype, while the NMDAR2B subtype was not involved.</p><p><strong>Conclusion: </strong>Esketamine suppressed proinflammatory microglial polarization by selectively modulating the NMDAR2A subtype, leading to the activation of the mTOR signaling pathway and enhancement of the BDNF-TrkB signaling pathway.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are adropin gene expression levels a precursor to type 2 diabetes mellitus in prediabetic patients?","authors":"Zeynep Yürekli-Sarar, Meral Urhan-Küçük, Edip Uçar, Gülay Gülbol-Duran, Emre Dirican, Seçkin Boz","doi":"10.1007/s11033-026-12965-7","DOIUrl":"10.1007/s11033-026-12965-7","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the relationship between adropin and glucose metabolism by evaluating ENHO gene expression and serum adropin levels in individuals with Type 2 diabetes mellitus (T2DM), prediabetes, and healthy controls, and their potential as biomarkers for early diagnosis.</p><p><strong>Methods: </strong>A total of 107 participants were enrolled, including 40 T2DM patients, 26 with prediabetes, and 41 healthy controls. Serum adropin levels were measured using ELISA, and ENHO gene expression levels were assessed by quantitative real-time PCR from peripheral blood samples. Biochemical parameters, including glucose, HbA1c, insulin, HOMA-IR, triglycerides, cholesterol, HDL, and LDL, were analyzed. Statistical comparisons between groups, correlation, logistic regression, and receiver operating characteristic analyses were conducted.</p><p><strong>Results: </strong>ENHO gene expression levels were significantly higher in the prediabetes group than in controls and T2DM, whereas it was lower in T2DM patients than in controls. Serum adropin levels were significantly elevated in the T2DM group compared with prediabetes and controls, but no difference was observed between prediabetes and controls. Glucose was negatively correlated with ENHO expression in prediabetes and with serum adropin in T2DM. ENHO expression was a significant predictor of T2DM progression, demonstrating high diagnostic potential.</p><p><strong>Conclusion: </strong>The findings suggest that ENHO gene expression level may increase in prediabetes as a compensatory mechanism, whereas it decreases in T2DM, indicating disease progression. The paradoxical elevation of serum adropin in T2DM may reflect metabolic alterations. ENHO expression could serve as a potential biomarker for identifying individuals at risk of developing T2DM, warranting further large-scale studies.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and functional interplay of prostaglandin F2 alpha and oxytocin in camel corpus luteum using in vitro model.","authors":"Zein Hussein, Sally Ibrahim, Karima Mahmoud, Mohamed Fathi, Faten F Mohammed, Tayseer I M Ismail","doi":"10.1007/s11033-026-12768-w","DOIUrl":"10.1007/s11033-026-12768-w","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the molecular and functional mechanisms of luteolysis in the mature camel corpus luteum (CL) in response to prostaglandin F₂ alpha (PGF), oxytocin (OXT), and their combination.</p><p><strong>Methods and results: </strong>CL from mature she-camel were obtained and in vitro cultured in a modified media, then subjected to hormonal treatments for 24 h, including prostaglandin (PFG; 1000 µM), oxytocin (OXT; 300 IU), or a combination thereof. The collected CL underwent RNA isolation and subsequent qRT-PCR analysis to assess the expression of key luteolytic genes: PTGFR, FASLG, and OXTR. Progesterone (P4) concentrations in the culture media were determined, and histological examinations were performed on the CL tissues. PGF treatment alone induced potent luteolysis, characterized by a significant reduction in P4 concentration (from 18.33 ± 2.85 to 5.44 ± 1.58 ng/mL), severe structural degeneration, and a marked four-fold upregulation of PTGFR and FASLG mRNA transcripts. Furthermore, OXT alone had no significant effect on P4 levels or gene expression. Crucially, the co-administration of PGF and OXT resulted in striking functional-structural dissociation: P4 secretion was maintained at control levels (18.43 ± 4.75 ng/mL), and the PGF-induced upregulation of PTGFR and FASLG was significantly attenuated (two-fold increase).</p><p><strong>Conclusion: </strong>OXT exerts a novel anti-luteolytic effect by interfering with the PGF-mediated molecular cascade, while the combination may simultaneously trigger a rapid, non-apoptotic structural collapse. This dissociation highlights a robust compensatory mechanism in the camel CL and suggests a potential therapeutic strategy for controlled luteal regression in camel breeding programs.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Virulence arsenal and antibiotic resistance backgrounds in Pseudomonas aeruginosa isolates from hospital wastewater samples from Iraq.","authors":"Farah H Omer, Noor S K Al-Khafaji, Batool Shakir Abed Almjalawi, Farah Tareq Al-Alaq, Hussein O M Al-Dahmoshi, Mushtak T S Al-Ouqaili, Faizan Ahmad, Morteza Saki","doi":"10.1007/s11033-026-12933-1","DOIUrl":"https://doi.org/10.1007/s11033-026-12933-1","url":null,"abstract":"","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuation of IL-8 expression following AHR inhibition in an in vitro model of intestinal inflammation.","authors":"Gilda Parsamanesh, Farshid Noorbakhsh, Kaveh Baghaei, Nima Rezaei","doi":"10.1007/s11033-026-12970-w","DOIUrl":"10.1007/s11033-026-12970-w","url":null,"abstract":"<p><strong>Background: </strong>The aryl hydrocarbon receptor (AHR) is an important regulator of intestinal homeostasis and has been linked to inflammatory bowel disease (IBD). However, its role in epithelial inflammatory responses is not fully understood. This study aimed to evaluate AHR signaling in in vitro models of intestinal inflammation and to investigate the effects of pharmacological AHR inhibition.</p><p><strong>Methods: </strong>Two inflammatory models were evaluated: a differentiated Caco-2/THP-1 co-culture system and a TNF-α/LPS-stimulated Caco-2 epithelial model. AHR expression was measured by real-time PCR. The model showing an AHR expression pattern consistent with our previous findings in pediatric IBD tissues was selected for further experiments. AHR was inhibited using BAY2416964, and the expression of TIPARP, IL-8, IL-6, and TNF-α was evaluated. IL-8 protein levels were also measured by ELISA.</p><p><strong>Results: </strong>AHR expression was significantly reduced in the Caco-2/THP-1 co-culture model but increased following TNF-α/LPS stimulation. Therefore, the TNF-α/LPS-stimulated Caco-2 model was selected for further experiments. BAY2416964 significantly reduced TIPARP expression, supporting effective inhibition of AHR signaling. AHR inhibition significantly reduced IL-8 mRNA expression, while reductions in IL-6 and TNF-α did not reach statistical significance. At the protein level, TNF-α/LPS significantly increased IL-8 production. BAY2416964 reduced IL-8 protein levels, although this reduction did not reach statistical significance.</p><p><strong>Conclusions: </strong>These findings suggest that AHR contributes to inflammatory responses in intestinal epithelial cells. Among the inflammatory mediators examined, IL-8 showed the most consistent response to AHR inhibition in this experimental model. The findings extend our previous observations of altered AHR expression by providing functional evidence for its involvement in epithelial inflammatory signaling. Further studies using complementary approaches and more physiologically relevant models are needed to define the broader functional significance of AHR inhibition in intestinal inflammation.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of the NAMPT/SIRT axis in HeLa cells exposed to adipose-derived mesenchymal stem cell-conditioned medium.","authors":"Mona Roozbehani, Somayeh Vafaei, Hossein Keyvani, Fatemeh Faraji, Minoo Tasbihi, Leila Masoori","doi":"10.1007/s11033-026-12873-w","DOIUrl":"10.1007/s11033-026-12873-w","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer cell survival depends on coordinated metabolic and stress response pathways. Adipose tissue-derived mesenchymal stem/stormal cells (AD-MSCs) release soluble factors and extracellular vesicle cargo that can alter tumor cell behavior, but their effects on the NAMPT/sirtuin axis in cervical cancer cells are not well defined. We therefore examined how AD-MSC-conditioned medium (CM) affects HeLa cell viability, apoptosis, and expression of NAMPT, SIRT1, SIRT2, and SIRT7.</p><p><strong>Methods: </strong>Previously isolated, characterized, and cryopreserved human AD-MSCs were thawed, expanded, and used to prepare CM. HeLa cells were exposed to 10%-100% CM for 48 h, and viability was measured by MTT assay. The 20% and 60% CM conditions were then evaluated by Annexin V/PI flow cytometry and qRT-PCR. NAMPT, SIRT1, SIRT2, and SIRT7 transcripts were quantified relative to GAPDH.</p><p><strong>Results: </strong>CM exposure reduced HeLa cell viability, with an estimated IC50 at 38.99%. The 20% condition increased the apoptotic cell fraction, whereas the response to 60% CM was not significant. At 20% CM, SIRT2 (p = 0.0036) expression decreased, SIRT7 expression increased (p = 0.0036), SIRT1 (p = 0.6286) and NAMPT(p = 0.3277) expression did not differ significantly from the comparison groups.</p><p><strong>Conclusion: </strong>Under the conditions tested, AD-MSC-CM reduced HeLa cell viability and promoted apoptosis most clearly at 20% CM. The accompanying decrease in SIRT2 and increase in SIRT7 point to a paracrine response involving metabolic and sirtuin related signaling. Identification of the active CM components and confirmation at the protein, enzyme-activity, and pathway levels are required before a causal mechanism can be assigned.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of ventromedial hypothalamic nucleus GAD gene knockdown on growth hormone-releasing hormone neuron transcriptomic profile in female rats.","authors":"Subash Sapkota, Madhu Babu Pasula, Rajesh Yadav, Karen P Briski","doi":"10.1007/s11033-026-12946-w","DOIUrl":"10.1007/s11033-026-12946-w","url":null,"abstract":"<p><strong>Background: </strong>Recent studies in male rats identify ventromedial hypothalamic nucleus (VMN)-dorsomedial division (VMNdm) growth hormone-releasing (Ghrh) neurons as a potential target for VMN γ-aminobutyric acid (GABA) control of counterregulatory hormone secretion.</p><p><strong>Methods and results: </strong>Current research used a female rat model to examine whether GABA regulation of eu- and/or hypoglycemic Ghrh neuron metabolic sensor, counterregulatory transmitter, and estrogen receptor (ER) gene profiles and contra-regulatory endocrine function is sex-dimorphic. Intra-VMN glutamate decarboxylase-2 (GAD2/GAD65) siRNA administration amplified transcripts encoding counterregulatory-enhancing neuropeptide (Ghrh) or enzyme marker proteins (glutaminase, neuronal nitric oxide synthase) in laser-catapult-microdissected Ghrh neurons from vehicle (V)- or insulin (INS)-injected females. Conversely, GAD2 siRNA down-regulated eu- and hypoglycemic GAD1 mRNA profiles. Steroidogenic factor-1 transcripts were correspondingly unaffected or inhibited in GAD2 siRNA pretreated V- versus INS-injected rats. VMN GAD2 gene knockdown up-regulated Ghrh neuron 5'-AMP-activated protein kinase alpha1 and - 2 gene expression in eu- and hypoglycemic animals. GAD2 siRNA caused glucose-dependent changes in lactate and estrogen receptor mRNA expression as gene knockdown inhibited transcription in euglycemic females while amplifying these gene profiles during hypoglycemia. GAD2 siRNA administration attenuated hypoglycemic hypercorticosteronemia and -glucagonemia and reversed down-regulated growth hormone (GH) secretion.</p><p><strong>Conclusions: </strong>Present findings importantly document female-specific GABA regulation of VMNdm Ghrh neuron metabolic signal reception, energy monitoring, and counterregulatory neurotransmitter release, as well as sex-dimorphic VMN GABAergic control of baseline (corticosterone, glucagon, GH) and hypoglycemic (GH) hormone outflow. Ongoing studies aim to discover how GABA-dependent input from these distinctive neurons to the female glucostatic neural network may affect counterregulation in that sex.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinically isolated hearing loss as a mild phenotype of PEX26-associated peroxisomal biogenesis disorder: A case report, literature review, and in silico analysis.","authors":"Fateme Zahedi Abghari, Emran Esmaeilzadeh, Marzieh Mohseni, Behrouz Robat-Jazi, Sajjad Biglari, Fatemeh Astaraki, Hamid Reza Khorram Khorshid, Reza Najafipour","doi":"10.1007/s11033-026-12878-5","DOIUrl":"10.1007/s11033-026-12878-5","url":null,"abstract":"<p><strong>Background: </strong>Peroxisome disorders result from impaired peroxisomal function and exhibit a broad spectrum of clinical phenotypes. Recent studies suggest that mutations in PEX26, accounting for approximately 3% of cases, contribute to a clinical spectrum ranging from severe neonatal forms to clinically isolated hearing loss (CIHL), a recently recognized phenotype.</p><p><strong>Methods: </strong>Whole-exome sequencing and copy-number variation (CNV) analysis were performed to identify the genetic basis of bilateral SNHL without any other clinical manifestations in an Iranian man. A comprehensive literature review was also conducted to contextualize our findings.</p><p><strong>Results: </strong>We identified a homozygous PEX26 variant, c.266G > T (p.Gly89Val), in the proband, segregating with the disease in the family. In silico analyses provided computational evidence supporting a potentially deleterious effect of the variant. Sixty-one reported cases of PEX26-related disorders were identified through a literature review, with Arg98Trp being the most frequent (30%). Most variants clustered in exons 2-3 and the cytoplasmic domain.</p><p><strong>Conclusion: </strong>This study identifies a novel PEX26 variant in a family with hearing loss without overt extra-auditory manifestations at the time of evaluation and provides preliminary evidence suggesting a possible association between PEX26 dysfunction and auditory phenotype.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic modulation of inflammation and oxidative stress in rheumatoid arthritis through Choerospondias axillaris intervention: evidence from in-vitro and in-vivo studies.","authors":"Sonia Mann, Debolina Chakraborty, Ashish Sarkar, Ankita Sharma, Swati Malik, Arindam Dey, Mohd Saquib, Lovely Joshi, Sagarika Biswas","doi":"10.1007/s11033-026-12893-6","DOIUrl":"10.1007/s11033-026-12893-6","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder, and current therapeutic approaches often present adverse effects on human health. This highlights the need to explore dietary sources of bioactive compounds for RA management. This study aimed to evaluate the potential of a Choerospondias axillaris (C. axillaris) chewable nutraceutical tablet (LT), formulated from the underutilized fruit of C. axillaris, for RA management.</p><p><strong>Methods: </strong>LTs were prepared by direct compression using C. axillaris fruit powder as the principal ingredient. The tablets were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). Antioxidant activity was evaluated using the DPPH free-radical scavenging assay. Potential RA-associated targets of C. axillaris were predicted using PharmMapper, followed by Cytoscape-based network analysis and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Selected targets were evaluated in synovial fibroblasts using quantitative PCR (qPCR) and in a collagen-induced arthritis (CIA) rat model. Molecular docking was performed to assess interactions between major bioactive compounds and selected RA-related proteins.</p><p><strong>Results: </strong>The formulated tablets contained detectable mineral elements and phytochemical constituents. Network pharmacology identified 20 potential targets associated with C. axillaris activity against RA. Molecular docking revealed potential interactions between selected bioactive compounds and key RA-related proteins. In vitro treatment reduced MAPK14, MMP9, and IL2 expression in synovial fibroblasts. In vivo treatment also suppressed inflammatory responses in the plasma of CIA rats.</p><p><strong>Conclusions: </strong>These findings indicate that C. axillaris bioactive compounds may modulate molecular targets associated with RA-related inflammation. The findings support further investigation of C. axillaris-derived nutraceutical formulations for RA management.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel approaches to target prostate cancer stem cells driving therapy resistance and cancer progression.","authors":"Fatema S Alatawi","doi":"10.1007/s11033-026-12948-8","DOIUrl":"10.1007/s11033-026-12948-8","url":null,"abstract":"<p><p>Prostate cancer remains one of the most common malignancies in men, and its global burden continues to rise. Although androgen deprivation therapy and other standard treatments can provide substantial disease control, advanced tumors may progress to castration-resistant prostate cancer, which is associated with poor outcomes. Preclinical and translational evidence implicates prostate cancer stem-like cells (PCSCs) in treatment persistence, progression, and relapse, without establishing them as the sole cause of resistance in patients. PCSC-associated states share functional traits with normal stem cells, including self-renewal and survival under stress; reduced androgen receptor activity occurs in some, but not all, stem-like populations. Their behavior is influenced by the genomic context, including PTEN loss, TP53/RB1 alterations, SPOP mutations, and TMPRSS2-ERG rearrangements, as well as hypoxia, stromal interactions, and inflammatory signaling. These alterations are not specific markers of PCSC identity. Multiple interconnected pathways, notably PI3K/AKT/mTOR, RAS/MAPK, Hedgehog, Wnt/β-catenin, Hippo, JAK/STAT, Notch, EGFR, and hypoxia-driven HIF signaling, provide candidate therapeutic targets. Additional strategies include modifying the microenvironment to suppress epithelial-to-mesenchymal plasticity, restoring tumor-suppressive microRNAs, and developing checkpoint inhibitors, vaccines, and CAR-T cells against relevant tumor-associated antigens. Most PCSC-specific evidence remains experimental, even when a pathway-directed agent has clinical activity or regulatory approval in a molecularly selected prostate cancer population. Clinical tumor responses do not by themselves demonstrate selective PCSC depletion. This narrative review distinguishes mechanistic findings from clinical outcomes and considers limitations involving marker specificity, model selection, drug delivery, toxicity, and therapeutic escape. Functionally validated biomarkers and appropriately designed combination trials are needed to determine whether targeting PCSC-associated states can improve durable disease control.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}