Journal of Cellular and Molecular Medicine最新文献

{"title":"Exploring the Potential of Calebin-A in Targeting Obesity-Related Genes and Pathways.","authors":"Ali Mahmoudi, Ali Saeedi-Boroujeni, Sercan Karav, Prashant Kesharwani, Amirhossein Sahebkar","doi":"10.1111/jcmm.71244","DOIUrl":"10.1111/jcmm.71244","url":null,"abstract":"<p><p>Obesity is a global health crisis affecting millions, associated with metabolic disorders such as type 2 diabetes and cardiovascular disease. Calebin-A, a bioactive compound derived from Curcuma species, has shown promise in managing obesity and its complications. This study utilized bioinformatics tools to explore the molecular mechanisms of Calebin-A in obesity. Transcriptomic data from obese and normal omental adipose tissue (GSE286454) were analysed, identifying 317 differentially expressed genes (DEGs). Functional enrichment analysis indicated a notable engagement of lysosomal activity, immune response, cell migration, axon guidance and apoptosis pathways. A STRING-based protein-protein interaction network revealed nine hub genes through a composite centrality score. Among these, CTSB, CTSZ, CTSA, GRN and TUBB exhibited upregulation and were prioritized for subsequent analysis. External validation (GSE59034; 16 obese vs. 16 controls) corroborated the consistent upregulation of CTSB, CTSZ, GRN and CTSA. Target prediction analysis identified 443 potential targets for Calebin-A, with pathway-level overlap suggesting a convergence on immune, lysosomal and cytoskeletal processes. Molecular docking studies indicated favourable binding affinities (-5.2 to -7.1 kcal/mol), with CTSZ demonstrating the most robust interaction. A 100 ns molecular dynamics simulation validated structural stability and indicated favourable binding free energy (MM-PBSA ΔG ≈ -110 kJ/mol). Results suggest that Calebin-A targets genes and proteins involved in energy balance and inflammation, offering insights into its anti-obesity potential. These findings provide a foundation for experimental validation and therapeutic development.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 11","pages":"e71244"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Cucurbitacin I in Colon Adenocarcinoma Is Mediated by Modulation of SDHA Expression.","authors":"Danni Zhao, Xunzhi Zhang, Wenke Xiao, Yue Lin, Zhixiang Wu, Xinyu Tang, Qian Cheng, Pengmian Feng, Wei Chen","doi":"10.1111/jcmm.71231","DOIUrl":"10.1111/jcmm.71231","url":null,"abstract":"<p><p>Colorectal cancer is a prevalent malignancy, with colon adenocarcinoma (COAD) representing its most common histological subtype. Although most stage I patients remain disease-free after treatment, a subset rapidly progresses to advanced disease with markedly reduced survival. Therefore, identifying early molecular warning signals in stage I patients is essential for timely intervention. In this study, integrated datasets from The Cancer Genome Atlas and Genotype-Tissue Expression projects were analysed using the landscape dynamic network biomarker (l-DNB) approach to identify progression biomarkers (PBs) for COAD. Twenty PBs were identified, among which succinate dehydrogenase complex flavoprotein subunit A (SDHA) was selected for further investigation. The L1000CDS² database was subsequently queried utilizing these identified PBs, identifying Cucurbitacin I (CuI) as a promising therapeutic component against COAD. Molecular docking and molecular dynamics simulations demonstrated stable binding between CuI and SDHA, with a binding energy of -9.44 kcal/mol and an RMSD of 2.0 ± 0.3 Å. Subsequent in vitro experiments demonstrated that CuI treatment upregulated SDHA expression and inhibited activation of the NF-κB pathway. Collectively, these findings suggest that the identified PBs may serve as early-warning indicators for stage I COAD patients and that CuI suppresses COAD cell proliferation, potentially through the SDHA/NF-κB axis, highlighting its promise as a potential therapeutic candidate.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 11","pages":"e71231"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA Metabolism Genes as Prognostic Biomarkers and Therapeutic Targets in Colorectal Cancer Based on the Analysis of Single-Cell and Bulk-RNA Sequencing Data.","authors":"Fandong Kong, Xuewei Zhang, Shuguang Su, Feilong Chen, Qiantao Ye, Ronghua Yang, Hanpeng Du","doi":"10.1111/jcmm.71236","DOIUrl":"10.1111/jcmm.71236","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most common malignancies worldwide and remains a major cause of cancer-related mortality. Increasing evidence suggests that aberrant RNA metabolism contributes to tumour initiation, progression and therapeutic resistance. In this study, we integrated single-cell RNA sequencing and bulk transcriptomic data to identify RNA metabolism-related genes (RMRGs) associated with CRC progression and evaluate their clinical significance. Through comprehensive bioinformatics analyses, 39 differentially expressed RMRGs were identified, with high RMRG activity predominantly enriched in epithelial cell populations. Cell-cell communication analysis revealed enhanced interactions between epithelial cells and other cell types within the tumour microenvironment. Further integration of single-cell and bulk RNA-sequencing datasets identified PCBP3 and NGRN as key prognostic genes. A two-gene prognostic model based on PCBP3 and NGRN was established and validated in independent cohorts, demonstrating favourable predictive performance. Human Protein Atlas data further confirmed the expression of both proteins in colorectal cancer tissues. Immune infiltration analyses indicated that PCBP3 and NGRN were associated with distinct immune-cell infiltration patterns and immunotherapy-related immune status. Functional experiments demonstrated that silencing PCBP3 or NGRN significantly inhibited the proliferation and invasion of HCT116 colorectal cancer cells. Moreover, Western blot analysis suggested that these effects may be mediated, at least in part, through regulation of the PI3K/AKT signalling pathway. Collectively, our findings identify PCBP3 and NGRN as promising prognostic biomarkers and potential therapeutic targets in colorectal cancer and provide new insights into the role of RNA metabolism in colorectal cancer progression and tumour immune regulation.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 11","pages":"e71236"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13253610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox Imbalance and NOS-Dependent Modulation of Superoxide in the Bladder Mucosa of Women With IC/BPS: A Preliminary Study.","authors":"Mariana G de Oliveira, Edson Antunes, Gabriela Reolon Passos, Luiz Gustavo Oliveira Brito, Carlos Arturo Levi D'Ancona, Fabíola Z Monica","doi":"10.1111/jcmm.71245","DOIUrl":"10.1111/jcmm.71245","url":null,"abstract":"<p><p>Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic condition characterized by bladder/pelvic pain and urinary symptoms, with poorly defined mechanisms and no reliable biomarkers. Oxidative stress, particularly reactive oxygen species (ROS), has been implicated in its pathophysiology, but direct human evidence remains scarce. Here, we evaluated ROS- and nitric oxide (NO)-related pathways in bladder mucosa from women with IC/BPS (n = 5) and controls (n = 7). Gene expression of NO-cGMP components, NADPH oxidases (NOX1-5), and antioxidant enzymes was assessed by qPCR. Baseline NO and superoxide ( <math> <semantics> <mrow><msubsup><mi>O</mi> <mn>2</mn> <mo>-</mo></msubsup> </mrow> <annotation>$$ {mathrm{O}}_2^{-} $$</annotation></semantics> </math> ) levels were quantified using histochemical assays, and the effects of pharmacological inhibitors of NOS, iNOS and NOX enzymes were examined. IC/BPS samples displayed increased expression of PDE5A (3.1-fold) and p47phox (1.6-fold), along with reduced SOD1 expression (0.39-fold), consistent with an oxidative imbalance. Although baseline <math> <semantics> <mrow><msubsup><mi>O</mi> <mn>2</mn> <mo>-</mo></msubsup> </mrow> <annotation>$$ {mathrm{O}}_2^{-} $$</annotation></semantics> </math> did not differ between groups, NOS inhibition with L-NAME markedly reduced <math> <semantics> <mrow><msubsup><mi>O</mi> <mn>2</mn> <mo>-</mo></msubsup> </mrow> <annotation>$$ {mathrm{O}}_2^{-} $$</annotation></semantics> </math> generation, with a greater effect in IC/BPS tissue (85% reduction). Conversely, selective iNOS inhibition (1400 W) increased <math> <semantics> <mrow><msubsup><mi>O</mi> <mn>2</mn> <mo>-</mo></msubsup> </mrow> <annotation>$$ {mathrm{O}}_2^{-} $$</annotation></semantics> </math> levels in IC/BPS biopsies. These findings suggest altered NOS-dependent redox regulation in the IC/BPS mucosa. Despite the limited sample size inherent to human biopsy studies, these results provide preliminary evidence of redox dysregulation in IC/BPS mucosa and highlight <math> <semantics> <mrow><msubsup><mi>O</mi> <mn>2</mn> <mo>-</mo></msubsup> </mrow> <annotation>$$ {mathrm{O}}_2^{-} $$</annotation></semantics> </math> as a relevant mediator. They support further investigation into therapeutic strategies targeting NOS redox balance and cGMP signalling.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 11","pages":"e71245"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13259972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148225392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β, β-Dimethylacrylshikonin Triggers Caspase-Mediated Cell Apoptosis via Heme Oxygenase-1 Upregulation and ERK/p38 Activation in Prostate Cancer.","authors":"Wei-Chun Weng, Yi-Hsien Hsieh, Chih-Hsin Tang, Shian-Shiang Wang, Chun-Chuan Su, Shih-Chi Su, Shun-Fa Yang","doi":"10.1111/jcmm.71241","DOIUrl":"10.1111/jcmm.71241","url":null,"abstract":"<p><p>β, β-Dimethylacrylshikonin (DMAS), a natural naphthoquinone derivative isolated from the root of a biennial herb belonging to the family Boraginaceae, has been demonstrated to exhibit anti-cancer and anti-inflammatory features. Yet, the effects of DMAS on restraining the progression of prostate cancer (PC) remain mostly elusive. Here, we attempted to examine whether DMAS hampers PC progression and subsequently explored the underlying mechanisms. Our results demonstrate that DMAS elicited cytotoxicity to PC cell lines, DU-145 and PC-3 cells, along with promotion of apoptosis and cell cycle arrest. Moreover, fluctuations in the levels of many potential apoptosis markers (upregulation of HO-1 and downregulation of cIAP-1 and XIAP) and activation of caspase pathways were observed in DMAS-treated PC cell lines. Furthermore, DMAS-induced caspase activations in PC cells were affected by silencing of HO-1 and the pretreatment with a selective ERK (U0126) or p38 inhibitor (SB203580), unveiling a functional linkage of HO-1, ERK, and p38 signalling to the responses of DMAS-treated PC cells. In conclusion, our results revealed that DMAS induced activation of caspase cascades to elicit cell apoptosis in PC, through HO-1 upregulation and ERK/p38 activation. These findings provide possible avenues for the use of a naturally occurring compound with therapeutic values in fighting prostate carcinogenesis.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 11","pages":"e71241"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13247124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hierarchical Disruption of the Tryptophan-Melatonin Axis Contributes to Glioma Progression Through AKT/ERK/STAT3 Signalling.","authors":"Bo Tan, Suqiu Yao, Shuangyin He, Tao Chen, Han Chen, Wenfu Yang, Xiyuan Tang, Tingting Xu, Jiajie Zhang, Xiaohong Yin, Ying Chen, Peng Song","doi":"10.1111/jcmm.71243","DOIUrl":"10.1111/jcmm.71243","url":null,"abstract":"<p><p>Melatonin signalling, mediated by membrane receptors and tightly regulated biosynthetic enzymes, is a key component of circadian and neuroendocrine control in the brain. However, whether the tryptophan-melatonin axis remains hierarchically intact during glioma progression and how its disruption affects downstream signalling remain unclear. In this study, transcriptomic data from TCGA, CGGA, and GTEx were integrated to characterize the expression patterns of melatonin receptors (MTNR1A and MTNR1B) and biosynthetic enzymes (AANAT and ASMT) across normal brain tissue, lower-grade glioma and glioblastoma. Protein expression was validated by immunohistochemistry, and functional consequences were investigated through gain- and loss-of-function experiments in glioma cells, followed by proliferation, migration, invasion, apoptosis and signalling analyses. Multi-layered analyses revealed a coordinated disruption of the tryptophan-melatonin axis during glioma progression. Expression of AANAT, ASMT, MTNR1A and MTNR1B progressively declined with increasing tumour grade and was associated with poor prognosis. Immunohistochemistry confirmed reduced MTNR1A and ASMT protein expression in glioma tissues. Restoration of these factors suppressed glioma cell proliferation, migration and invasion while promoting apoptosis. Mechanistically, these effects were accompanied by inhibition of AKT, ERK and STAT3 signalling. These findings demonstrate that hierarchical disruption of receptor- and synthesis-dependent melatonin signalling is a defining molecular feature of glioma and may contribute to malignant progression through activation of AKT/ERK/STAT3 pathways, providing new insights into the biological and therapeutic relevance of the tryptophan-melatonin axis in glioma.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 11","pages":"e71243"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Landscape and Tumour Heterogeneity in Ovarian Cancer: Insights From Single-Cell RNA Sequencing.","authors":"Sihan Chen, Ghada Moh Samir Elhessewi, Helen Cai, Wedad M Alawad, Manoj Kumar Mishra, Usamah Sayed","doi":"10.1111/jcmm.71235","DOIUrl":"10.1111/jcmm.71235","url":null,"abstract":"<p><p>Tumour heterogeneity is a key factor in cancer progression, with immune responses within the tumour microenvironment (TME) contributing significantly to treatment resistance and immunotherapy outcomes. Recent advances in single-cell RNA sequencing (scRNA-seq) have provided unprecedented insights into the diverse immune cell populations infiltrating tumours, including both innate immune cells like dendritic cells, neutrophils, macrophages, and natural killer (NK) cells, as well as adaptive immune cells such as T lymphocytes. The immune landscape of tumours is complex and dynamic, characterised by a mixture of activated and suppressed immune states that evolve over time. The degree of immune cell infiltration varies among tumour types and disease stages, influencing tumour response to therapies. For example, ovarian cancer typically exhibits weaker immune infiltration compared to cancers like melanoma and non-small cell lung cancer. Increased CD8+ T cell infiltration is generally associated with favourable prognosis, while elevated regulatory T cells (Tregs) can suppress anti-tumour immune responses. The use of scRNA-seq has enabled detailed profiling of immune cells, revealing the roles of exhausted T cells and immunosuppressive macrophages in the TME. This high resolution approach facilitates the identification of distinct immune cell subsets and their functional states, providing a platform for developing more targeted, personalised immunotherapies. The findings offer promising avenues for improving clinical outcomes in ovarian cancer and other malignancies through refined immune profiling.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 11","pages":"e71235"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13259974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148225445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid Cell Function and Cytokine Profiles in Paediatric Haemophilia A: Insights From FVIII and Emicizumab Prophylaxis.","authors":"Alessia Cottonaro, Saicharan Akula, Berardino Pollio, Irene Ricca, Tiziano Martini, Roberto Albiani, Jacopo Agnelli Giacchello, Patrizia Sciancalepore, Roberto Santi, Antonia Follenzi, Simone Merlin","doi":"10.1111/jcmm.71216","DOIUrl":"10.1111/jcmm.71216","url":null,"abstract":"<p><p>Haemophilia A (HA) is an X-linked bleeding disorder caused by factor VIII (FVIII) deficiency, treated with FVIII infusions or, more recently, Emicizumab subcutaneously. Although Emicizumab is safe and effective, FVIII is still required for severe bleeding, trauma, or surgery, and few studies have compared these prophylactic options in paediatric patients. This study explores the immunological and haematological profiles of paediatric HA patients receiving FVIII or Emicizumab, using haemophilia B patients and healthy controls. Clinical parameters and immune cell populations showed no major differences aside from age-related variations. However, HA patients displayed higher HLA-DR expression on CD14⁺ cells than healthy controls, and Emicizumab-treated patients showed increased HLA-DR expression on CD11c⁺ cells compared with FVIII-treated patients. Plasma cytokines including IL-12p40, TNF-α, CCL-22, IL-18, and CCL-4 were elevated in HA, suggesting a dysregulated myeloid compartment in HA. Patient-derived macrophages exhibited a stronger pro-inflammatory (M1-like) polarization after in vitro FVIII stimulation, with increased TNF-α and reduced TGF-β gene expression. Stratification by prophylaxis showed that macrophages from FVIII-treated patients maintained the M1 phenotype, whereas those from Emicizumab-treated patients showed no clear shift and tended toward an immune-regulatory profile. These findings highlight distinct myeloid and cytokine signatures associated with different prophylaxis, emphasizing the need for optimized therapeutic strategies.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 11","pages":"e71216"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin Signalling-Inducible IFITM1 Promotes Multiple Myeloma Progression and Bortezomib Resistance.","authors":"Ji-Young Lim, Yeojin Kim, Sung-Soo Park, Jungyeon Lee, Chang-Ki Min","doi":"10.1111/jcmm.71183","DOIUrl":"10.1111/jcmm.71183","url":null,"abstract":"<p><p>Insulin substantially promotes the growth of malignant cells that overexpress the insulin receptor (INSR), and insulin excess has been recognised as a cancer-promoting factor in patients. Interferon-induced transmembrane protein 1 (IFITM1) is also overexpressed in various cancers. In this study, we investigate the association between insulin signalling-induced IFITM1 expression and multiple myeloma (MM) aggressiveness. We observed that expression of both INSR and IFITM1 was significantly elevated in symptomatic MM patients compared with those with monoclonal gammopathy of undetermined significance (MGUS) and smouldering MM (SMM). Notably, IFITM1-but not INSR-expression correlated with prognosis following autologous stem cell transplantation and bortezomib-based induction therapy. Further analysis revealed that IFITM1 expression in bone marrow plasma cells was associated with the concentrations of insulin and insulin-like growth factor 2 (IGF-II) in the bone marrow microenvironment. Insulin and IGF-II enhanced MM cell proliferation through IFITM1 upregulation, whereas suppression of IFITM1 abrogated the proliferative effects of these ligands. Moreover, insulin and IGF-II attenuated apoptosis and the inhibition of cell migration induced by the proteasome inhibitors (PIs) bortezomib and carfilzomib, and these effects were reversed by IFITM1 knockdown. The ability of insulin to reduce bortezomib-induced apoptosis and G2/M phase cell cycle arrest was likewise dependent on IFITM1 expression. Collectively, these findings suggest that insulin-induced IFITM1 plays a pivotal role in MM progression and resistance to bortezomib, highlighting IFITM1 as a potential prognostic biomarker and therapeutic target.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 11","pages":"e71183"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FTO-Catalysed Demethylation of LUR1 mRNA Suppresses Macrophage Lipid Accumulation and Aortic Atherosclerosis.","authors":"Xiang-Yang Tang, Le Zhou, Shu-Jun Li, Shao-Xiang Zhang, Yue-Ying Yuan, Yun-Cheng Lv","doi":"10.1111/jcmm.71234","DOIUrl":"10.1111/jcmm.71234","url":null,"abstract":"<p><p>Lipid deposition and foam cell formation drive atherogenesis. Lipid uptake regulator 1 (LUR1) and N6-methyladenosine (m6A) modification play key roles in systemic lipid homeostasis. Bioinformatic analyses revealed a negative correlation between fat mass and obesity-associated protein (FTO) and LUR1 expression and abundant m6A sites within the LUR1 mRNA strand. We therefore hypothesized that FTO-catalysed demethylation modulates LUR1 expression and lipid accumulation in macrophages, thereby influencing aortic plaque development. Acetylated low-density lipoprotein-loaded THP-1 macrophages were transduced with recombinant lentiviruses, and FTO and LUR1 expression was determined by Western blotting and qPCR. m6A abundance was measured by methylated RNA immunoprecipitation-qPCR. Intracellular lipids were quantified by ELISA, and lipid droplets (LDs) were quantified using Oil Red O (ORO) staining. The plasma lipid concentration, aortic sinus plaque area and lipid deposition were evaluated by biochemical assays and histological staining in high-fat-fed apoE^-/- mice that received recombinant adeno-associated viruses. The results revealed that elevated FTO expression not only reduced LUR1 expression and its m6A modification and decreased intracellular LD and cholesterol ester contents but also significantly decreased plasma triglyceride (TG) and low-density lipoprotein-cholesterol levels (LDL-C) and decreased the aortic lesion area. Co-overexpression of FTO and LUR1 abolished these protective effects. These findings indicate that FTO-erased m6A modification decreases LUR1 expression in macrophages to inhibit intracellular lipid accumulation and the occurrence of atherosclerosis (AS).</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"30 11","pages":"e71234"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13259957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148225397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}