JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Identification of ceRNA Regulatory Networks Driven by the lncRNA NEAT1 in Multiple Myeloma","authors":"Domenica Ronchetti,&nbsp;Valentina Traini,&nbsp;Ilaria Silvestris,&nbsp;Giuseppina Fabbiano,&nbsp;Andrea Devecchi,&nbsp;Federica Torricelli,&nbsp;Noemi Puccio,&nbsp;Ilaria Craparotta,&nbsp;Marco Bolis,&nbsp;Roberto Piva,&nbsp;Antonino Neri,&nbsp;Luca Agnelli,&nbsp;Francesco Passamonti,&nbsp;Niccolò Bolli,&nbsp;Elisa Taiana","doi":"10.1111/jcmm.71123","DOIUrl":"10.1111/jcmm.71123","url":null,"abstract":"<p>The lncRNA NEAT1 is overexpressed in multiple myeloma (MM) plasma cells and plays a key role in MM pathogenesis. NEAT1 is involved in ceRNA network in several cancers; however, data in MM are virtually absent. This study identified a NEAT1-driven ceRNA network involving 96 miRNAs and 40 target genes, selected as concurrently downregulated in NEAT1-KD AMO1 cells and upregulated in NEAT1-overexpressing AMO1 cells (AMO1-OVX). The co-expression of NEAT1 and the targets was validated in MM patients (GSE116294, GSE13591, GSE6477, CoMMpass), and in NEAT1-KD NCI-H929, LP1, and KMS27 cell lines, showing for all targets a consistent downregulation, resembling that of NEAT1. The functional implication of the ceRNA network was explored by functional enrichment analyses of the 40 targets, identifying 78 significant gene sets, 17 of which were found significantly enriched by GSEA analysis in at least one experimental condition among NEAT1-KD LP1, NCI-H929, and KMS27 cells, AMO1-OVX cells, or the extreme quartiles of NEAT1 expression in the CoMMpass dataset. Noteworthy, the cell cycle gene set was validated in 5 out of 6 conditions tested, suggesting that in MM the impact of NEAT1 upregulation on the cell cycle, experimentally demonstrated in our earlier publications, may be attributable, at least partially, to ceRNA mechanisms.</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/PMC13051828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609004","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 Ferroptosis With Natural Products for the Treatment of Skeletal System Disease: An Updated Review","authors":"Qian Yi,&nbsp;Jinye Li,&nbsp;Guotian Luo,&nbsp;Jiachen Li,&nbsp;Dahang Yang,&nbsp;Wei Sun,&nbsp;Weichao Sun,&nbsp;Wei You,&nbsp;Lei Yang","doi":"10.1111/jcmm.71106","DOIUrl":"10.1111/jcmm.71106","url":null,"abstract":"<p>Skeletal system diseases, encompassing chronic disorders of the skeletal system which commonly include osteoarthritis, rheumatoid arthritis, osteoporosis and osteosarcoma. Their incidence rates have been increasing in recent years, resulting in significant social and economic burdens. However, their pathogenesis remains inadequately explored. Ferroptosis, a recently identified form of regulated cell death, differs from other cell death mechanisms, such as apoptosis and autophagy, by primarily involving iron metabolism and lipid peroxidation. The underlying mechanism of ferroptosis is characterised by intracellular iron overload and accumulation of ROS, both of which contribute to the onset of osteoarthritis, rheumatoid arthritis and osteoporosis and are closely linked to the malignancy of osteosarcoma. To enhance understanding of ferroptosis' potential role in the pathophysiology and treatment of skeletal system diseases, this review examines its relationship with these conditions, the mechanisms involved and the therapeutic potential of natural compounds in modulating ferroptosis. By investigating the contribution of ferroptosis to the occurrence and progression of these diseases, novel clinical targets for diagnosis and treatment are proposed.</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/PMC13051910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608945","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":"Targeted Therapies in Infantile Hemangiomas and Vascular Malformations: From β-Blockers to PI3K/AKT/mTOR Inhibitors","authors":"Hubert Arasiewicz,&nbsp;Michal Dec","doi":"10.1111/jcmm.71103","DOIUrl":"10.1111/jcmm.71103","url":null,"abstract":"<p>Vascular tumours and malformations encompass infantile hemangiomas (IHs) and genetically driven vascular malformations with distinct natural histories and therapeutic vulnerabilities. The discovery that the non-selective beta-blocker propranolol induces rapid regression of proliferating IHs established the first widely adopted systemic pharmacologic therapy in vascular anomaly care and provided a clinical proof-of-concept that targeting lesion-specific endothelial biology can alter disease course. In parallel, recurrent somatic variants affecting PI3K/AKT/mTOR (e.g., PIK3CA, TEK/TIE2, AKT1) and RAS/MAPK (e.g., KRAS, NRAS) signalling have reframed many malformations as mosaic disorders amenable to targeted inhibition with agents such as sirolimus, alpelisib, AKT inhibitors and MEK inhibitors. This review synthesizes translational mechanisms, clinical evidence and safety considerations for beta-blockers and emerging targeted therapies, emphasizing lesion phenotype, timing of intervention and molecular stratification as determinants of response. We highlight current limitations, including toxicity, durability and pathway escape, and outline future directions for precision therapy and genotype-guided trial design in vascular anomalies.</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/PMC13052144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608942","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":"Correction to “Endogenous Hormone 2-Methoxyestradiol Suppresses Venous Hypertension-Induced Angiogenesis Through Up- and Down-Regulating p53 and ID-1”","authors":"","doi":"10.1111/jcmm.71100","DOIUrl":"10.1111/jcmm.71100","url":null,"abstract":"<p>X. Zou, L. Zhang, J. Yuan, et al., “Endogenous Hormone 2-Methoxyestradiol Suppresses Venous Hypertension-Induced Angiogenesis Through Up-and Down-Regulating p53 and ID-1,” <i>Journal of Cellular and Molecular Medicine</i> 22(2018): 957–967. https://doi.org/10.1111/jcmm.13399</p><p>In Xiang Zou et al. one immunohistochemistry panel of Figure 3B was misplaced in Figure 1A due to a technical error during image preparation. The correct Figure 1 is shown below. The authors confirm all results and conclusions of this article remain unchanged.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574163","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":"NR3C1 Modulates Wnt Signalling to Influence the Invasiveness and Immune Features of Nonfunctioning Invasive Pituitary Adenomas","authors":"Xiaoping Wang,&nbsp;Jinfeng Zhang,&nbsp;Tao Jiang,&nbsp;Zhijun Yang,&nbsp;Yu Zhang,&nbsp;Pinan Liu,&nbsp;Yuanxiang Lin","doi":"10.1111/jcmm.71097","DOIUrl":"10.1111/jcmm.71097","url":null,"abstract":"<p>Pituitary adenomas (PAs) are common intracranial tumours, and invasiveness in nonfunctioning invasive pituitary adenomas (NIPAs) predicts poor prognosis. The molecular mechanisms driving this phenotype remain unclear. This study explored the role of nuclear receptor subfamily 3 group C member 1 (NR3C1) in NIPA invasiveness and its regulation of Wnt signalling. mRNA expression profiles of 32 PA samples were generated by RNA-seq, and proteomic data from 19 samples were obtained by mass spectrometry. Immune-related differentially expressed genes (DEGs) were retrieved from GeneCards. Weighted gene coexpression network analysis identified modules and hub genes linked to invasiveness, while machine learning methods (support vector machine, LASSO, random forest) prioritised key genes. Gene set enrichment analysis (GSEA) assessed pathways associated with candidate gene expression. NR3C1 expression and function were validated by immunohistochemistry, Western blotting and invasion assays. Integration of transcriptomic, proteomic and immune-related datasets yielded 11 overlapping genes, with NR3C1 emerging as the top candidate. NR3C1 was significantly upregulated in NIPAs and demonstrated good discriminatory power by ROC analysis. GSEA associated high NR3C1 expression with Wnt pathway activation. Functional experiments confirmed that NR3C1 overexpression enhances the invasive capacity of PA cells. NR3C1 promotes the invasive phenotype of NIPAs by activating Wnt signalling. These findings suggest NR3C1 as a potential biomarker and therapeutic target for invasive pituitary adenomas.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147573097","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":"CRB2 Facilitates Epithelial Ovarian Cancer Progression by Inducing Polarity Changes via Activation of the Wnt/PCP Signalling Pathway","authors":"Chunlin Tao,&nbsp;Shaojing Li,&nbsp;Duohe Sun,&nbsp;Jun Zhou,&nbsp;Yuanping Chen,&nbsp;Rong Zhang,&nbsp;Xiaoge Ni","doi":"10.1111/jcmm.71124","DOIUrl":"10.1111/jcmm.71124","url":null,"abstract":"<p>Ovarian cancer exhibits high molecular heterogeneity and metastatic potential, contributing to its status as a leading cause of gynecologic cancer mortality. Cell polarity is essential in tumorigenesis, yet the role of Crumbs family proteins (CRBs), key regulators of apical–basal polarity, in epithelial ovarian cancer (EOC) remains unclear. In this study, we analysed CRB expression profiles using TCGA and GEO datasets, and validated our findings through immunohistochemical staining of ovarian tumour tissue microarrays. Among CRBs, CRB2 was significantly overexpressed in EOC tissues and correlated with poor patient prognosis. Functional assays revealed that CRB2 enhances ovarian cancer cell proliferation, migration, and invasion, while suppressing apoptosis. Immunofluorescence staining of planar cell polarity markers demonstrated that CRB2 induces polarity alterations in EOC cells. Furthermore, Western blot analysis suggested that CRB2 may activate the Wnt/planar cell polarity (PCP) signalling pathway, contributing to tumour progression. These findings identify CRB2 as a key modulator of cell polarity and a potential driver of EOC aggressiveness. CRB2 may serve as a novel prognostic biomarker and therapeutic target for epithelial ovarian cancer.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574150","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":"Single-Cell Transcriptomic Analysis of Chemotherapy-Induced Changes in Osteosarcoma With a Pyroptosis-Related Gene-Based Prognostic Model","authors":"Tao Jin,&nbsp;Lei Dong,&nbsp;Wang Kai,&nbsp;Ziyang Yu,&nbsp;Guoyong Yu,&nbsp;Weifeng Liu","doi":"10.1111/jcmm.71110","DOIUrl":"10.1111/jcmm.71110","url":null,"abstract":"<p>Osteosarcoma, the most common primary malignant bone tumour, presents significant treatment challenges due to its complex tumour microenvironment and the development of chemoresistance. This study employs single-cell transcriptomics to investigate chemotherapy-induced changes in osteosarcoma at both the cellular and molecular levels. Single-cell RNA sequencing data were analysed to identify cell subpopulations and their responses to chemotherapy. Differential gene expression and pathway enrichment analyses were performed to elucidate chemotherapy-induced changes. Additionally, we developed and validated a predictive model based on pyroptosis-related genes, named Pyroscore, using 101 different machine-learning algorithms. Chemotherapy led to an increased proportion of osteoclasts, endothelial cells, mesenchymal stem cells and pericytes, while decreasing T and NK cells, B cells, chondroblasts, monocytes and macrophages. Chemotherapy markedly upregulates the pyroptosis pathway in tumour cells, suggesting that chemotherapy induces programmed cell death in cancer cells through the activation of pyroptosis. Metabolic pathway analysis revealed significant inhibition of sulphur metabolism, starch and sucrose metabolism, pentose phosphate pathway, inositol phosphate metabolism, nitrogen metabolism and fatty acid metabolism. The Pyroscore model, which incorporates BAK1, CASP1, CASP5 and CASP6, demonstrated robust prognostic value across multiple data sets, with high scores correlating with improved survival outcomes. This study highlights the impact of chemotherapy on osteosarcoma cell subpopulations and the tumour microenvironment. The activation of the pyroptosis pathway and the development of the pyroscore prognostic model provide new insights into the mechanisms of chemotherapy response and potential therapeutic targets. These findings underscore the importance of personalized treatment strategies in improving outcomes for osteosarcoma patients.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529355","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":"Mitochondria-Related Pathogenic Genes in Paediatric Asthma: A Multi-Omics Mendelian Randomization Study","authors":"Biyu Zhang,&nbsp;Yaqin Li,&nbsp;Bo Ding,&nbsp;Xiaoyan Li,&nbsp;Yanming Lu","doi":"10.1111/jcmm.71102","DOIUrl":"10.1111/jcmm.71102","url":null,"abstract":"<p>Mitochondrial dysfunction is implicated in asthma pathogenesis, but causal roles of mitochondrial-related genes in paediatric asthma remain unclear. We performed a multi-omics Mendelian randomization study integrating GWAS data from paediatric asthma cohorts with blood-based methylation quantitative trait loci (mQTLs), expression QTLs (eQTLs) and protein QTLs (pQTLs) datasets. Causal inference was assessed using Summary-data-based Mendelian Randomization (SMR) and HEIDI testing, complemented by colocalization analysis. Findings were validated in independent cohorts and evaluated for tissue specificity using GTEx. Functional enrichment and protein–protein interaction (PPI) network analyses were conducted. SMR analysis identified 80 methylation sites spanning 54 genes, 26 gene expressions, and three proteins significantly associated with paediatric asthma. Colocalization analysis confirmed strong evidence for 10 methylation sites (7 genes), the <i>STX17</i> eQTL (PP.H4 = 0.98) and the <i>UNG</i> pQTL (PP.H4 = 0.84). Tissue-specific eQTL validation replicated the <i>STX17</i> association. Multi-omics integration associated <i>ALAS1</i> (cg13241645, cg15698299) and <i>TXNRD1</i> (cg09884423) with asthma at both methylation and expression levels, with colocalization supporting both <i>ALAS1</i> associations. Furthermore, integrated mQTL-eQTL analysis suggests that DNA methylation potentially regulates <i>ALAS1</i> and <i>TXNRD1</i> expression. Functional enrichment and network analyses revealed that these candidate genes converge on mitochondrial metabolic pathways and identified seven hub genes with potential regulatory significance (<i>SDHB, MFN2, GLDC, PHB2, TXNRD1, ATP5MC1</i> and <i>PHB</i>). This study provides multi-omics evidence supporting a causal role for mitochondrial-related genes, particularly <i>ALAS1</i> and <i>TXNRD1</i>, in paediatric asthma, offering new insights into pathogenesis and potential therapeutic targets.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529340","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":"Wine-Processed Cornus officinalis Ameliorates Osteoarthritis via Modulating M1/M2 Macrophage Polarization","authors":"Yongsheng Fu,&nbsp;Minghua Zhao,&nbsp;Xudong Huang,&nbsp;Yingchao Ren,&nbsp;Weiguo Wang","doi":"10.1111/jcmm.71113","DOIUrl":"10.1111/jcmm.71113","url":null,"abstract":"<p><i>Cornus officinalis</i> (CO) is a traditional herbal medicine renowned in Traditional Chinese Medicine (TCM) for its properties of tonifying the liver and kidney and replenishing vital essence. Meanwhile, wine-processed CO (pCO) exhibits superior pharmacological effects, including anti-inflammatory, antioxidant and anti-fibrotic activities. However, the immunomodulatory mechanism of pCO in osteoarthritis (OA) remains unclear. OA models were established in Sprague–Dawley rats via anterior cruciate ligament transection (ACLT). Network pharmacology and molecular docking were used to predict potential targets of pCO against OA, which were validated through behavioural tests, histomorphological staining and immunohistochemistry. HPLC-Q-Orbitrap-MS analysis identified key differential compounds between raw and wine-processed CO. The immunomodulatory effects of pCO were further confirmed by ELISA, immunofluorescence staining and RT-qPCR. pCO ameliorated joint pain and cartilage damage in OA rats by reducing pro-inflammatory factors (IL-1β, COX-2, IL-12) and promoting anti-inflammatory factors (IL-10, TGF-β1) in serum and synovial fluid. Network pharmacology combined with in vivo experiments revealed that pCO attenuated chondrocyte degeneration and apoptosis. Mechanistically, pCO modulated macrophage polarization by suppressing the M1 phenotype (CD86, iNOS) while promoting the M2 phenotype (CD206, TGF-β1, Arg-1), which revealed the key mechanism underlying its therapeutic effects against OA. pCO improved joint function and attenuated cartilage degeneration and synovial lesions, which were associated with the promotion of articular cartilage protection via the modulation of M1/M2 macrophage polarization.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529325","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":"Inactivation of CDK12 Enhances Mitochondrial Efficiency to Suppress DNA Damage","authors":"Aishwarya Gondane,&nbsp;Shivani Yalala,&nbsp;Jing Liang,&nbsp;Sonja Saira,&nbsp;Harri M. Itkonen","doi":"10.1111/jcmm.71101","DOIUrl":"10.1111/jcmm.71101","url":null,"abstract":"<p>Inactivation of cyclin-dependent kinase 12 (CDK12) characterizes a subset of prostate cancers but it is not understood how cells adapt to declining activity of this major transcription elongation kinase. To probe this response, we developed a cell line resistant to an inhibitor targeting CDK12 and its paralog, CDK13. CDK13 can compensate for the loss of CDK12, which is why we used the dual inhibitor THZ531. Targeted drug screening of the parental and resistant cell lines revealed cross-resistance to other transcriptional kinases but no clear acquired point of vulnerability. Using genome-wide mapping of mRNA-stabilization based on metabolic labelling of RNA, we report selective mRNA stabilization of factors promoting oxidative phosphorylation in the resistant cells. We go on to show that loss of CDK12 activity enhances ATP production both in cell line models and in patient tumours. Finally, we show that dual inhibition of CDK12/13 results in excessive phosphorylation of the DNA damage H2AX in prostate cancer cells but not in our CDK12/13 inhibitor-resistant model system. In brief, we propose that inactivation of <i>CDK12</i> rewires cellular energy metabolism to suppress DNA damage.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 7","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529298","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}