JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"The GPCR Connection: Linking Alzheimer's Disease and Glioblastoma","authors":"Ana B. Caniceiro,&nbsp;Sofia P. Agostinho,&nbsp;Luiz F. Piochi,&nbsp;Nícia Rosário-Ferreira,&nbsp;Irina S. Moreira","doi":"10.1111/jcmm.71131","DOIUrl":"10.1111/jcmm.71131","url":null,"abstract":"<p>Alzheimer's disease (AD) and glioblastoma multiforme (GBM) are biologically distinct age-related brain disorders with opposing clinical phenotypes. AD is characterised by progressive neurodegeneration and cognitive decline, whereas GBM is characterised by aggressive cellular proliferation and a poor prognosis. Despite these differences, converging evidence indicates that both conditions share molecular pathways and network-level dysfunction that emerge during brain ageing. Central to this convergence are G protein-coupled receptors (GPCRs), which act as integrative signalling hubs that regulate inflammation, metabolism, calcium (CA²⁺) homeostasis, and cell survival. In AD, GPCR signalling modulates amyloid-β production and clearance, Tau phosphorylation, intracellular CA²⁺ dynamics, and glial-driven neuroinflammation. In contrast, the same receptor families promote tumour growth, angiogenesis, immune evasion, and therapeutic resistance in patients with GBM. Core intracellular cascades, such as PI3K-AKT–mTOR and MAPK–ERK, are dysregulated in both diseases and function as shared signalling backbones, with outcomes dictated by cellular context rather than receptor identity. CXCR4, LPA₁, and FPR1 exemplify this duality, driving either oncogenic proliferation or neuronal dysfunction, depending on the biological environment. Recent advances in integrative multiomics, computational modelling, artificial intelligence, and organoid systems have revealed GPCR-centred regulatory nodes and accelerated the identification of druggable targets. Collectively, these findings suggest that AD and GBM, although pathologically antithetical, share a molecular fingerprint shaped by ageing-associated inflammation, metabolic disruption, cellular senescence and dysregulated GPCR networks. Deciphering this context-dependent duality may enable precision therapeutic strategies to either restore neuronal integrity in AD or suppress malignant programmes in GBM while fostering cross-fertilisation between neurodegeneration and neuro-oncology research.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABCB1 Polymorphisms Influence on Temozolomide Resistance and Overall Survival in Glioblastoma Patients: A Systematic Review of Clinical Evidence","authors":"Fabiola De Luca,&nbsp;Deborah Mannino,&nbsp;Anna Paola Capra,&nbsp;Giuliana Ciappina,&nbsp;Marco Donato,&nbsp;Giuseppe Caruso,&nbsp;Emanuela Esposito,&nbsp;Alessio Ardizzone","doi":"10.1111/jcmm.71130","DOIUrl":"10.1111/jcmm.71130","url":null,"abstract":"<p>Glioblastoma (GB), defined as IDH-wildtype CNS WHO grade 4 tumour according to the 2021 WHO classification of CNS tumours, remains a uniformly lethal malignancy in which the efficacy of temozolomide (TMZ) continues to be constrained by both intrinsic tumur biology and the pharmacological barrier imposed by the blood–brain barrier (BBB). Given the central role of the ABCB1 (MDR1/P-glycoprotein) efflux transporter in regulating CNS drug disposition, germline variation in ABCB1 has been proposed as a potential determinant of interindividual variability in TMZ response. This systematic review synthesised clinical evidence from four independent studies, encompassing more than 400 GB patients, evaluating the association between ABCB1 polymorphisms and TMZ efficacy and patients' survival. Across the available literature, the influence of ABCB1 genetic variation emerged as limited and inconsistent. An early study reported a marked survival advantage for carriers of the ABCB1 C1236T C/C genotype treated with TMZ, suggesting reduced efflux and enhanced drug exposure. However, subsequent investigations, including epigenetic analyses, high-quality multivariate survival modelling and a pharmacokinetic study demonstrating genotype-dependent differences in plasma TMZ concentrations, did not replicate a corresponding survival effect. Across the remaining cohorts, common variants such as 1236C&gt;T, 2677G&gt;T/A, 3435C&gt;T and 1199G&gt;A showed no robust association with clinical outcome, indicating that transporter-mediated modulation is likely overshadowed by dominant prognostic drivers, including MGMT methylation, IDH status and tumour heterogeneity. Collectively, current evidence does not support ABCB1 polymorphisms as reliable predictive biomarkers of TMZ response in GB. Nonetheless, the pharmacokinetic signals observed, together with emerging technologies capable of selectively modulating efflux activity at the tumour–BBB interface, point to a continued role for ABCB1 in future therapeutic strategies. Integration of transporter genomics with spatial pharmacokinetics and molecular stratification will be essential to refine drug delivery and improve outcomes in GB.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent Mechanisms of Cranial Suture Ossification in Normal Development and Pathologic Fusion","authors":"Anvith Reddy,&nbsp;Sarah Qaddo,&nbsp;Penny Li,&nbsp;Barite Gautama,&nbsp;Erin Abbott,&nbsp;Yomna Dean,&nbsp;Anna Means,&nbsp;Michael Golinko,&nbsp;Christopher Bonfield,&nbsp;Wesley Thayer,&nbsp;Galen Perdikis,&nbsp;Matthew Pontell","doi":"10.1111/jcmm.71125","DOIUrl":"10.1111/jcmm.71125","url":null,"abstract":"<p>Cranial sutures are dynamic growth sites that balance bone growth with mesenchymal patency to accommodate cranial expansion during development. While intramembranous ossification has traditionally been considered the default mechanism of suture fusion, accumulating evidence demonstrates that endochondral pathways might also play a significant role under both physiological and pathological conditions. In this review, we contrast normal developmental ossification processes with premature fusion in craniosynostosis, integrating histological, molecular, and imaging data. We highlight the context-dependent nature of cranial suture biology, influenced by embryonic origin, local signalling gradients, and genetic perturbations. Recognizing divergent ossification mechanisms reframes our understanding of both normal and premature suture fusion and has clinical implications for mechanism-specific therapeutic strategies. Finally, we outline areas for future investigation, including high-resolution profiling of human sutures across developmental stages, to establish a normative framework for cranial suture biology and inform mechanism-driven regenerative approaches.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCT7 Regulates TRAF6-Mediated Autophagy to Promote Posttraumatic Joint Contracture","authors":"Yutai Li,&nbsp;Wenhui Zhang,&nbsp;Wenbin Xu,&nbsp;Yuliang Huang,&nbsp;Honghua Cai,&nbsp;Nanwei Zhang,&nbsp;Tangzhao Liang,&nbsp;Guihua Liu","doi":"10.1111/jcmm.71051","DOIUrl":"10.1111/jcmm.71051","url":null,"abstract":"<p>Posttraumatic joint contracture (PTJC) is a prevalent complication of joint injury, characterised by marked reductions in both active and passive joint motion. Previous studies have indicated that the chaperonin-containing T-complex polypeptide (CCT) is involved in fibrotic processes. Thus, this study aims to explore the role of CCT7 in PTJC and clarify its underlying regulatory mechanisms. We found that CCT7 expression was significantly upregulated in PTJC joint tissues and in fibroblasts stimulated with TGF-β1. Knockdown of CCT7 markedly reduced the expression of α-SMA and COL-I and suppressed fibroblast migration, while simultaneously promoting autophagy, as indicated by increased LC3-II and Beclin-1 levels and decreased p62 expression, thereby alleviating joint fibrosis. Interestingly, CCT7 interacted with TRAF6 to facilitate its ubiquitination and degradation. Knockdown of TRAF6 reversed the promoting effect of CCT7 knockdown on autophagy in fibroblasts and exacerbated fibrosis. Consistently, in vivo experiments demonstrated that CCT7 knockdown improved joint range of motion, reduced the expression of fibrosis-related proteins, enhanced autophagy and ultimately alleviated fibrosis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting BCL-xL in Myeloid Malignancies: From Inhibitors to PROTAC","authors":"Daniela Cilloni,&nbsp;Alessandro Ferrando,&nbsp;Francesco Frassoni","doi":"10.1111/jcmm.71036","DOIUrl":"10.1111/jcmm.71036","url":null,"abstract":"<p>Restoring apoptosis in malignant cells represents a central goal of anticancer therapy. Tumour cells often escape cell death by overexpressing anti-apoptotic members of the BCL-2 protein family, particularly BCL-2, BCL-xL, and MCL1. These proteins inhibit the intrinsic mitochondrial apoptotic pathway through intricate interactions with pro-apoptotic partners and direct modulation of the mitochondrial outer membrane. Their pivotal role in cell survival has established them as attractive therapeutic targets. Over the past two decades, significant efforts have been devoted to developing selective small-molecule inhibitors capable of neutralising these proteins and reactivating apoptosis. A first milestone was the discovery of ABT-263 (navitoclax), a dual BCL-2/BCL-xL inhibitor. Building on this achievement, the development of venetoclax, a highly selective BCL-2 inhibitor, marked a major breakthrough, demonstrating potent pro-apoptotic activity and clinical efficacy in several leukaemia subtypes. Despite these advances, the design of inhibitors of BCL-2 family members remains challenging, largely due to the structural characteristics of the BH3-binding groove, which is both shallow and hydrophobic, complicating the identification of molecules with optimal binding affinity and selectivity. PROTACs targeting BCL-xL may represent a promising future strategy, potentially overcoming the intrinsic limitations of small molecule inhibitors.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Expression Alterations Associated With Resveratrol-Induced Antiproliferative Effects and S-Phase Cell Cycle Arrest in Osteosarcoma Cancer Cells","authors":"Raffaella De Pace,&nbsp;Maria Rosa Iaquinta,&nbsp;Roberta Chiarelli,&nbsp;Maria Giulia Dell'Aquila,&nbsp;Fabio Casciano,&nbsp;Cinzia Brenna,&nbsp;Elisa Mazzoni","doi":"10.1111/jcmm.71111","DOIUrl":"10.1111/jcmm.71111","url":null,"abstract":"<p>Osteosarcoma (OS) is an aggressive primary bone tumour with high metastatic potential. Current treatments including surgery and chemotherapy are limited by side effects and chemoresistance, underscoring the need for novel therapies. This study aimed to investigate the antitumor potential of resveratrol (RSV), a natural polyphenol, as a novel treatment for OS. The effects of RSV were evaluated in two osteosarcoma cell lines (SAOS-2 and U2-OS). A viability assay established 100 μM as the effective concentration, and hyperspectral imaging confirmed cellular uptake. Apoptosis was measured via caspase-3/7 activity and Annexin V/PI staining, while qRT-PCR assessed pro-apoptotic gene expression. Flow cytometry evaluated cell-cycle progression, and a wound-healing assay measured migration. Gene expression analyses (qRT-PCR) examined markers of cell adhesion, tumour progression and epithelial–mesenchymal transition. Finally, RSV's impact on the Wnt/β-catenin pathway was determined by quantifying nuclear β-catenin accumulation and the expression of its downstream oncogenic targets. RSV inhibited cell proliferation and induced apoptosis, increasing caspase-3/7 activity and modulating apoptotic gene expression. RSV also caused cell cycle arrest in S-phase. It reduced the cells' migration and altered the expression of cell adhesion and tumour progression genes, promoting a less invasive phenotype. Notably, RSV decreased nuclear β-catenin accumulation, downregulated oncogenic targets like c-Myc and MMPs, and upregulated E-cadherin while reducing vimentin levels, suggesting a reversal of epithelial–mesenchymal transition. These results suggest that RSV may offer a promising therapeutic approach for osteosarcoma, modulating key pathways involved in tumour progression, metastasis and chemoresistance. Further studies are required to assess its clinical applicability.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OMICS Profiling Identifies Signatures of Senescence in Osteogenesis Imperfecta Osteoblasts Counteracted by 4-PBA","authors":"Roberta Besio,&nbsp;Elisa Maffioli,&nbsp;Erika Palladino,&nbsp;Alessandra Sala,&nbsp;Nadia Garibaldi,&nbsp;Valerio Izzi,&nbsp;Antonella Forlino,&nbsp;Gabriella Tedeschi","doi":"10.1111/jcmm.71120","DOIUrl":"10.1111/jcmm.71120","url":null,"abstract":"<p>Mutations in collagen I are the most common cause of osteogenesis imperfecta (OI), leading to delayed protein folding and structurally abnormal molecules. While some aberrant collagen is secreted into the extracellular matrix (ECM), impairing bone quality, a significant fraction is retained intracellularly, disrupting osteoblast homeostasis. 4-phenylbutyrate (4-PBA) has been shown to improve osteoblast function and ECM composition in OI models. To investigate the intracellular consequences of mutant collagen retention and the mechanisms of 4-PBA, we analysed the secretome and transcriptome of two dominant OI mouse models, <i>Col1a1</i>^{<i>+/G349C</i>} and <i>Col1a2</i>^{<i>+/G610C</i>}. MS/MS proteomic analysis of conditioned media revealed senescence-associated secretory phenotype proteins, together with components linked to altered cytoskeletal organization and cell adhesion. Transcriptomic analysis identified <i>P53</i> as a central hub gene, supporting premature senescence activation. Increased senescence-associated β-galactosidase activity, elevated expression of the cyclin-dependent kinase inhibitor <i>P16</i>, and reduced <i>Ki67</i> levels further supported a senescent phenotype. Notably, senescence-associated proteins were absent from the secretome following 4-PBA treatment, which also modulated cytoskeletal and adhesion-related protein expression. Moreover, 4-PBA significantly reduced senescence marker expression and decreased the number of senescent cells. Overall, these findings indicate that cellular senescence underlies osteoblast dysfunction in OI and uncover a novel contribution of 4-PBA to osteoblast homeostasis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DAPK1-Mediated Parkin Inactivation Enhances Neurotoxicity via MITOL-Dependent Degradation","authors":"Chul Hong Park,&nbsp;Donghyuk Shin,&nbsp;Kwang Chul Chung","doi":"10.1111/jcmm.71132","DOIUrl":"10.1111/jcmm.71132","url":null,"abstract":"<p>Parkinson's disease (PD) is characterised by progressive neurodegeneration and is marked by the formation of Lewy bodies, which are intracellular aggregates primarily composed of <i>α</i>-synuclein. Mitochondrial dysfunction and impaired protein degradation pathways are thought to play critical roles in PD progression, contributing to the loss of dopaminergic neurons in the <i>substantia nigra</i>. Phosphorylation of <i>α</i>-synuclein has been shown to promote its aggregation, underscoring its potential role in disease progression. Parkin, an E3 ubiquitin ligase, is widely regarded as a pleiotropic neuroprotective protein that modulates the mitochondrial quality control, as well as metabolic turnover and the accumulation of <i>α</i>-synuclein. Death-associated protein kinase 1 (DAPK1), which is involved in the regulation of apoptosis and autophagy, has recently emerged as an important factor in neurodegeneration. While DAPK1 has been implicated in Alzheimer's disease through its role in tau aggregation and amyloid-<i>β</i> production, our findings suggest that DAPK1 may also influence PD-related pathways by phosphorylating parkin at Ser136 and Ser198. This phosphorylation promotes the mitochondrial transport of parkin, enhancing interaction with mitochondria-localised E3 ubiquitin ligase MITOL and consequently leading to the degradation of parkin. Given the neuroprotective role of parkin, its reduction increases the vulnerability of neurons to 6-hydroxydopamine-induced toxicity, potentially contributing to decreased neuronal survival. Together, these findings suggest that DAPK1 functions as a previously unrecognised modulator of parkin and could potentially influence PD-related neurodegenerative processes. This pathway may provide a mechanistic link between mitochondrial dysfunction, <i>α</i>-synuclein pathology and neuronal cell death.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIF-1α/Netrin-4 Axis Mediates RIPC-Induced Angiogenesis and Neurogenesis After Ischemic Stroke","authors":"Zhaowei Feng,&nbsp;Zhenqian Liu,&nbsp;Siyu Tang,&nbsp;Meihua Pan,&nbsp;Kaishen Zhu,&nbsp;Yiwei Liu,&nbsp;Chunyu Wang,&nbsp;Ruiqin Yao,&nbsp;Xiue Wei,&nbsp;Haiyan Liu","doi":"10.1111/jcmm.71121","DOIUrl":"10.1111/jcmm.71121","url":null,"abstract":"<p>Remote ischemic postconditioning (RIPC) confers neuroprotection in ischemic stroke partly via promoting angiogenesis and neurogenesis, but its precise molecular mechanisms remain unclear; here, we investigated the role of the secreted guidance protein Netrin-4 (NTN4) and its upstream regulator hypoxia-inducible factor 1α (HIF-1α) in mediating RIPC's reparative effects, using endothelial-specific Ntn4 knockout (KO) mice subjected to transient middle cerebral artery occlusion (MCAO) and RIPC, alongside in vitro assays with brain microvascular endothelial cells (BMECs) and neural stem cells (NSCs) and molecular interaction analyses, including DNA pull-down and chromatin immunoprecipitation (ChIP), finding that RIPC significantly upregulated NTN4 expression in the ischemic penumbra of MCAO mice, that endothelial-specific Ntn4 knockout abolished RIPC's protective effects—impairing neurological recovery, angiogenesis and neurogenesis, which were rescued by recombinant NTN4 administration, that NTN4 promoted BMEC proliferation and tube formation via an integrin β1-PI3K/AKT pathway while conditioned medium from Ntn4-overexpressing BMECs enhanced NSC neuronal differentiation through an integrin β1-MAPK/ERK axis, and that RIPC stabilised HIF-1α, which directly bound the Ntn4 promoter to drive its transcription, collectively establishing that RIPC orchestrates brain repair by stabilising HIF-1α to transcriptionally activate endothelial NTN4, which signals through integrin β1 to drive parallel PI3K/AKT and MAPK/ERK pathways for angiogenesis and neurogenesis, highlighting this axis as a key therapeutic target in stroke.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Prognostic and Predictive miRNA Biomarkers Shape the Landscape of T Cell Dysfunction in Cancer","authors":"Hong-jiu Wang,&nbsp;Xiao-ling Wen,&nbsp;Zhe-yu Wu,&nbsp;Na Wang,&nbsp;Shu-heng Fu,&nbsp;Fei-fan Xiong,&nbsp;Jiang-ying Liang,&nbsp;Deng-hui Guo,&nbsp;Si-rui Li,&nbsp;Jie Shen,&nbsp;Xiao-ling Gao,&nbsp;Zhen-zhen Wang","doi":"10.1111/jcmm.71117","DOIUrl":"10.1111/jcmm.71117","url":null,"abstract":"<p>T cell dysfunction (TCD) plays a critical role in cancer progression and significantly impacts patient outcomes. Despite its importance, the exact molecular mechanisms underlying TCD remain poorly understood. To address this, we constructed a comprehensive pan-cancer landscape of TCD, with a particular focus on identifying miRNA biomarkers that define and predict TCD severity. Our analysis revealed six key miRNAs (miR-203b, miR-214, miR-4772, miR-141, miR-200a, and miR-200b) that were closely associated with varying degrees of TCD. These prognostic miRNAs not only exhibited distinct expression patterns across four identified TCD subtypes (from low to high TCD severity) but also demonstrated strong predictive performance in classifying patients with different levels of TCD. The identified miRNA signatures serve as reliable biomarkers for stratifying patients into high-risk and low-risk groups, with higher TCD levels correlating to poorer overall survival. In addition to miRNA biomarkers, we observed that patients with severe TCD exhibited increased infiltration of immune cells and macrophages and dysregulation of DNA methylation patterns. Patients with higher degrees of TCD displayed low methylation levels, which further contributed to the progression of T cell dysfunction. In summary, our study highlights the pivotal role of miRNA biomarkers in shaping the landscape of T cell dysfunction across cancers. These miRNAs serve as both prognostic indicators and predictive tools, enabling accurate classification of TCD severity and offering new avenues for therapeutic exploration and patient stratification in cancer immunotherapy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}