Cell Biochemistry and Biophysics最新文献

{"title":"Retraction Note: Relationship between lncRNA MALAT1 and Chemo-radiotherapy Resistance of Cancer Cells: Uncovered Truths.","authors":"Ahmed Hjazi, Saade Abdalkareem Jasim, Farag M A Altalbawy, Harpreet Kaur, Hamza Fadhel Hamzah, Irwanjot Kaur, Mahamedha Deorari, Abhinav Kumar, Ahmed Elawady, Mohammed N Fenjan","doi":"10.1007/s12013-026-02058-4","DOIUrl":"10.1007/s12013-026-02058-4","url":null,"abstract":"","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"4685"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479425","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":"Mitigation of D-Galactose-Induced Aging in Mice by Cymbopogon citratus and Its Major Bioactive Compound.","authors":"Rimsha Abaidullah, Shaukat Ali, Asim Pervaiz, Farooq Ahmad","doi":"10.1007/s12013-026-02114-z","DOIUrl":"10.1007/s12013-026-02114-z","url":null,"abstract":"<p><p>The biological process of aging is a progressive decline in physical ability and is characterized by oxidative stress and inflammation across multiple organs. Plant phytochemicals have emerged as promising candidate for exhibiting strong antioxidant and anti-inflammatory properties. Cymbopogon citratus (Lemongrass) exhibits strong antioxidant and anti-inflammatory properties that might counteract the key mechanisms involved in aging. The current study investigates the antiaging potential of Cymbopogon citratus extract (CCE), Cymbopogon citratus-mediated silver nanoparticles (CCE-AgNPs) and Citral (Cit) in a D-galactose-induced aging mice model. In vivo evaluation was performed after inducing aging in mice by administering a dose of 250 mg per kg for 60 days continuously via intraperitoneal route followed by treatment with the respective test formulations. A dose of 250 mg per kg of CCE, 200 mg per kg dose of CCE-AgNPs, 200 mg per kg of Cit and 150 mg per kg of metformin was used a treatment. Different biochemical parameters revealed that out of all the treatments, CCE-AgNPs significantly resulting in peak values of CAT (148.6 ± 49.8 U/ml), SOD (157.2 ± 12.6 U/ml), GPx (43.0 ± 1.8 U/ml), GRx (23.0 ± 4.1 U/ml). Also, lower MDA, FSH and cortisol levels indicated strong antiaging potential of Cymbopogon citratus mediated AgNPs. Moreover, the histological findings of liver, brain and kidney of D-galactose group showed oxidative stress induced changes while CCE AgNPs improved the histopathological changes induced by D-galactose, making a potential future in antiaging research field.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"4197-4214"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590214","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":"RHBDD2 Confers Insensitivity of Esophageal Squamous Cell Carcinoma to Cisplatin by Inhibiting Ferroptosis Through the Wnt3a/β-Catenin/FTH1 Axis.","authors":"Youxiang Ding, Geng Tian, Minjie Zhang, Lin Zou","doi":"10.1007/s12013-026-02118-9","DOIUrl":"10.1007/s12013-026-02118-9","url":null,"abstract":"<p><p>As a pseudoprotease member of the rhomboid family, rhomboid domain containing 2 (RHBDD2) has been demonstrated to be associated with 5‑FU resistance. Our previous work found that RHBDD2 is also upregulated by cisplatin (DDP) treatment in esophageal squamous cell carcinoma (ESCC). However, the effect of RHBDD2 on DDP sensitivity and the underlying molecular mechanisms remain poorly understood. In this study, we demonstrate that RHBDD2 regulates the sensitivity of ESCC cells to DDP in vitro. In vivo, RHBDD2 knockdown significantly enhanced the antitumor effect of DDP in a subcutaneous xenograft model of ESCC. Enrichment analysis of RNA‑seq data from ESCC cells with RHBDD2 knockdown revealed that RHBDD2 is involved in regulating the biological process of ferroptosis. RHBDD2 inhibited ferroptosis by upregulating ferritin heavy chain 1 (FTH1), a major iron storage protein, and FTH1 knockdown reversed RHBDD2‑induced insensitivity of ESCC cells to DDP in vitro. Mechanistically, RHBDD2 promoted Wnt3a secretion, which in turn inhibited the phosphorylation and ubiquitination of β‑catenin, thereby enhancing β‑catenin nuclear localization and its transcriptional activity. Inhibition of β‑catenin‑mediated transcription by ICG‑001 reversed RHBDD2‑upregulated FTH1 expression and DDP insensitivity in vivo. Furthermore, we found that RHBDD2 mRNA is modified by N⁶‑methyladenosine (m⁶A), and its expression can be regulated by the m⁶A reader insulin‑like growth factor 2 mRNA‑binding protein 2 (IGF2BP2) in ESCC cells. Collectively, our results reveal a novel role for RHBDD2 in inhibiting ferroptosis and inducing DDP insensitivity by upregulating the Wnt3a/β‑catenin/FTH1 axis, which may provide a therapeutic target for improving the efficacy of DDP in ESCC.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"4273-4286"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429537","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":"Succinic Acid-Sunitinib Combination Treatment Downregulates the Angiogenic Gene Expressions in Sunitinib- Resistant Renal Cancer Cell Line.","authors":"Baris Ertugrul, Goksu Kasarci Kavsara, Sinem Bireller, Arzu Ergen, Bedia Cakmakoglu","doi":"10.1007/s12013-026-02129-6","DOIUrl":"10.1007/s12013-026-02129-6","url":null,"abstract":"<p><p>Drug resistance hinders treatment success in many cancers. Sunitinib is one of the first-line treatments in renal cell carcinoma (RCC), but resistance develops during treatment. By ameliorating their angiogenic ability, tumor cells finding a different route of escape in RCC is a majorconcern. We aimed to investigate the effects of the succinic acid sunitinib combination on the angiogenesis mechanism in sunitinib-resistant renal cancer cell lines. Gene expression levels of VEGF-A, VEGF-C, PDGF-A, HIF1A, TGF-β, VHL, ANGPT1, and TIE2; protein levels of VEGF-A, HIF1A, and VHL were compared before, and after succinic acid-sunitinib combination treatment in ACHN cells that developed sunitinib resistance. In the sunitinib-resistant group, HIF1A, TGF-β, ANGPT1, and TIE2 gene expression levels were significantly decreased with a combination therapy of succinic acid at 25 µMcompared to the resistant control group. Our study focused on clarifying the increase of angiogenic factors in sunitinib-resistant RCC cells following sunitinib treatment and the subsequent changes in the combination of succinic acid as a secondary treatment agent. It is also anticipated to guide future studies exploring the potential clinical application of the combination of sunitinib and succinic acid.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"4395-4407"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719705","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":"Long-Term Culture of U87MG Glioblastoma Cells Reprograms Metabolism, Impacts Aggressiveness and Alters Drug Responses.","authors":"Alina A Isakova, Nadezhda V Antipova, Diana V Mazur, Irina N Druzhkova, Alena I Gavrina, Margarita L Shuvalova, Olga I Patsap, Dmitry A Bondarenko, Arkadiy N Murashev, Mikhail P Kirpichnikov, Marine E Gasparian, Anne V Yagolovich, Dmitry A Dolgikh","doi":"10.1007/s12013-026-02121-0","DOIUrl":"10.1007/s12013-026-02121-0","url":null,"abstract":"<p><p>It is known that prolonged cell passaging may affect the outcomes of cell-based experiments. This study aimed to comprehensively investigate the consequences of long-term culture of U87MG glioblastoma cells, focusing on cell metabolism, morphology, tumorigenicity and drug response. U87MG (L) cells subjected to long-term culturing (20 passages) displayed altered morphology and significantly enhanced autofluorescence of lipofuscin, a well-established marker of oxidative stress and cellular senescence, compared with control U87MG cells maintained for only 5 passages. Fluorescence-lifetime imaging microscopy (FLIM) of NADH revealed the metabolic shift likely associated with glycolysis in long-term cultured U87MG (L) cells. Using the genetically encoded sensor HyPer7, the increase in basal intracellular levels of hydrogen peroxide in U87MG (L) cells was detected. In vivo studies employing orthotopic intracranial xenotransplantation in immunodeficient NSG mice revealed that, unlike short-term cultured U87MG cells, which formed visible tumor nodules with clearly delineated margins, long-term cultured U87MG (L) cells infiltrated diffusely into brain tissues, invaded bone tissue, and exhibited perineural growth. Such an aggressive behavior resulted in worse survival outcomes of xenograft-bearing mice. Notably, U87MG (L) cells became less susceptible to temozolomide, but acquired sensitivity to death receptor 5 (DR5)-selective variant of cytokine TRAIL in vitro and in vivo due to increased DR5 expression on the cell surface and downregulation of cFLIP expression. Our findings with the U87MG cell line indicate that culture duration can alter cellular responses, thereby impacting experimental outcomes. It should be carefully considered when establishing tumor models and evaluating efficacy of potential drug candidates.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"4321-4330"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766112","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 SERCA1a by Sesquiterpene Lactones: Insights into Inhibition Mechanisms.","authors":"Petronela Rezbáriková, Jana Viskupičová, Magdaléna Májeková, Silvia Micháliková, Michal Jurášek, Pavel Drašar, Juraj Harmatha, Eva Kmoníčková","doi":"10.1007/s12013-026-02097-x","DOIUrl":"10.1007/s12013-026-02097-x","url":null,"abstract":"<p><p>The sarcoplasmic reticulum Ca²⁺-ATPase (SERCA1a) is a key regulator of intracellular calcium homeostasis and an emerging therapeutic target in cancer, cardiac, and metabolic diseases. Sesquiterpene lactones such as thapsigargin (TG) and trilobolide (TB) inhibit SERCA1a via transmembrane binding, yet systematic comparisons of their inhibitory potency and biophysical mechanisms remain limited. Here, we investigated the inhibitory effects of TG, TB, and two TB derivatives (TB-44, TB-46(2)) using kinetic, thermodynamic, and docking analyses. SERCA1a activity in isolated sarcoplasmic reticulum vesicles was quantified by an NADH-coupled ATPase assay, with Ca²⁺- and ATP-dependence modeled by Michaelis-Menten and Hill fits. All compounds inhibited SERCA1a in a dose-dependent manner, with TB most potent (IC₅₀ = 0.36 µM vs. TG 0.60 µM) and TB-44 the most effective derivative (IC₅₀ = 1.47 µM). Each reduced V_max while largely preserving Ca²⁺ sensitivity, consistent with stabilization of a low-turnover SERCA1a conformation and impaired ATP-driven catalysis. Notably, TB's enhanced potency, despite intermediate calculated binding energy (ΔG = - 9.1 kcal/mol), correlated with moderate lipophilicity (logP = 2.43) and favorable electrostatic contacts with Gln259. These data highlight that effective SERCA1a inhibition by sesquiterpene lactones reflects an interplay between lipophilicity, membrane partitioning, and electrostatic-hydrophobic complementarity, rather than binding affinity alone.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3967-3979"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148215799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Ferroptosis-related Genes Associated with the Prognosis of Hepatocellular Carcinoma.","authors":"Kai Yan, Fangfang Hu, Haodong Tang, Jiahua Zhou","doi":"10.1007/s12013-026-02096-y","DOIUrl":"10.1007/s12013-026-02096-y","url":null,"abstract":"<p><p>Ferroptosis has been increasingly implicated in the progression of various tumors, including hepatocellular carcinoma (HCC). This study aimed to identify ferroptosis-related genes with prognostic significance in HCC. Differential expressed genes (DEGs) and long non-coding RNAs (DElncRNAs) were identified from TCGA LIHC RNA-seq data. A competitive endogenous RNA (ceRNA) network was established based on ferroptosis-related lncRNA-mRNA pairs. Prognostic genes were identified through survival analysis, and selected DEGs were further validated via quantitative PCR. Co-expression analysis identified 218 lncRNA-mRNA pairs, including 216 DEGs and 11 DElncRNAs. Among these, 11 upregulated ferroptosis-related genes were identified as predicted targets of the lncRNA DDX11-AS1. MiR-195 and miR-424 both regulated CDC25A and HELLS. Elevated expression of DDX11-AS1, CDC25A, EZH2, FANCD2, and HELLS was associated with poorer survival. In vitro cellular experiments showed that the knockdown of DDX11-AS1, CDC25A, and HELLS inhibited cell proliferation and invasion by promoting ferroptosis in Huh7 cells. The 11 ferroptosis-related genes and DDX11-AS1 may serve as valuable prognostic biomarkers and potential immunotherapeutic targets in HCC.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3951-3965"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148314910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Bronchial Receptors with Concentration-Response Curves, Bitterness Assessment, and Computer Simulations.","authors":"Mohamed Bouzid, Houda Smati, Yosra Ben Torkia, Sonia Bayouth, Abdellatif Sakly, Abdelmottaleb Ben Lamine","doi":"10.1007/s12013-026-02117-w","DOIUrl":"10.1007/s12013-026-02117-w","url":null,"abstract":"<p><p>This research aims to explore the human-like taste response of three bitter molecules (chloroquine, denatonium, and saccharin) on the human bronchi receptor T2R agonist using a statistical physics approach. By fitting the concentration-taste response curves, we estimate three model parameters (R_M, n, C_1/2) to assess the intermolecular interactions with T2R receptor sites. In addition, the transduction coefficient (α) of the three tasting molecules has been determined. This analysis provides valuable insights into the binding energy spectrum (AES) and establishes a common gustatory band for the bitter tastes, with adhesive energies distributed over a relatively wide range (2.5-22.5 kJ mol⁻¹). In addition, molecular docking simulations were conducted, revealing that denatonium exhibits stronger binding affinities (28.87 kJ/mol) with the T₂R₁₀ human taste receptor site compared to chloroquine (26.78 kJ/mol). Conversely, saccharin displayed a binding affinity of approximately 23.85 kJ/mol with the binding pocket of the T₂R₃₁ ion channel receptors. This three molecules undergoes theoretical analysis using the DFT/B3LYP/6-311 G(d, p) basis set to determine its frontier orbital features and stability. The type and strength of interactions were identified using the topological parameters of the \"Atoms in Molecules\" (AIM) method, NCI analysis was used to study intra- and intermolecular noncovalent interactions within a molecular system, as well as natural bond orbital (NBO) analysis. NBO analyses indicate that all three tasting molecules exhibits significant stability. NCI interaction analyses indicate that Van der Waals forces and steric effects are observed in the three tasting molecules. 3D shaded potential surface revealed a projection of LOL examination and the electron localization function (ELF) indicated that an area of electron depletion is observed in the three tasting molecules.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"4233-4272"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429523","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":"Comparative Transcriptomic Analysis Reveals Shared Interferon-Associated Transcriptional Programs and Subset-Associated Immune Variation in Human cDC1 and cDC2 Cells Following TLR7 Activation.","authors":"Vural Yilmaz","doi":"10.1007/s12013-026-02116-x","DOIUrl":"10.1007/s12013-026-02116-x","url":null,"abstract":"<p><strong>Background: </strong>Conventional dendritic cells (cDCs) are central regulators of antiviral immunity, translating Toll-like receptor signaling into coordinated gene expression programs. Human cDC subsets, including cDC1 and cDC2, exhibit distinct functional properties; however, the extent to which these subsets engage shared versus subset-associated transcriptional responses following Toll-like receptor 7 (TLR7) stimulation remains incompletely defined.</p><p><strong>Methods: </strong>We performed an in silico transcriptomic re-analysis of publicly available NanoString gene expression data derived from purified human cDC1 and cDC2 populations. Analytical approaches included global expression profiling, principal component analysis, exploratory differential gene expression analysis, and module-based functional profiling of interferon, inflammatory, and antigen presentation pathways. Additional analyses included comparative fold-change assessment and integrated co-expression network analysis of immune-associated genes.</p><p><strong>Results: </strong>Global transcriptomic analysis demonstrated clear segregation of samples by stimulation status and dendritic cell subset, with consistent clustering of biological replicates. TLR7 activation induced substantial transcriptional remodeling in both subsets, with differences in the magnitude and distribution of regulated genes. Functional module analysis revealed stimulation-associated shifts in interferon-related and inflammatory transcriptional organization across both cDC1 and cDC2 cells, together with subset-associated variation in the relative magnitude and coordination of immune-associated transcriptional responses. Gene-level analysis further indicated strong induction of several canonical interferon-responsive genes, including ISG15, MX1, IFIT1, STAT1, and IRF7, in cDC2 cells, whereas cDC1 cells demonstrated comparatively more heterogeneous relative expression changes for several interferon-associated transcripts. Inflammatory mediators such as IL12B, TNF, CXCL10, and CCL3 likewise exhibited subset-associated variation in relative transcriptional responses. Integrated co-expression and hierarchical clustering analyses further suggested that TLR7-responsive immune genes form partially coordinated transcriptional networks rather than strictly isolated subset-specific pathways. In contrast, antigen presentation-related genes remained comparatively stable across conditions.</p><p><strong>Conclusions: </strong>TLR7 stimulation is associated with partially shared interferon-associated transcriptional organization across human cDC subsets, accompanied by subset-associated variation in inflammatory and immune transcriptional responses, highlighting overlapping but non-identical innate immune activation architectures across dendritic cell subsets.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"4215-4231"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429567","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":"Resveratrol Modulates Lung Cancer-Associated Hub Genes Identified by Integrated Bioinformatics, Single-Cell Analysis, Molecular Docking, and Experimental Validation.","authors":"Jinghua Yang, Hanxiu Wei, Jie Li, Jun Chen","doi":"10.1007/s12013-026-02142-9","DOIUrl":"10.1007/s12013-026-02142-9","url":null,"abstract":"<p><p>Lung cancer remains a major cause of cancer-related mortality, and reliable molecular targets with therapeutic relevance are still needed. This study aimed to identify key genes associated with lung cancer progression and explore the potential regulatory effect of resveratrol. The GSE43458 dataset, including 80 lung cancer samples and 30 control samples, was used for differential expression analysis and weighted gene co-expression network analysis (WGCNA). Intersecting genes were subjected to protein-protein interaction network construction, Cytoscape-based hub gene screening, functional enrichment analysis, and immune infiltration analysis. Single-cell RNA sequencing data from GSE131907 were further analyzed to characterize cellular heterogeneity and hub gene distribution. Resveratrol was predicted as a candidate compound, followed by molecular docking with hub proteins. Finally, CCK-8, Western blotting, and qRT-PCR assays were performed in BEAS-2B and A549 cells. A total of 1,655 differentially expressed genes were identified, and WGCNA identified the 252-gene turquoise module as the module most strongly associated with the lung cancer phenotype (r = - 0.86, P = 6.0 × 10⁻³⁵). Intersection analysis yielded 250 candidate genes, representing 15.1% of all differentially expressed genes. Five hub genes, CASP3, DDX54, TP53BP1, CDKN2A, and ABT1, were identified and showed significantly increased expression in lung cancer tissues (P < 0.05). Functional enrichment analysis linked the candidate genes to apoptosis, cell-cycle regulation, DNA damage repair, immune responses, and cancer-related pathways, while immune infiltration and single-cell analyses revealed marked remodeling of immune and stromal components. Molecular docking predicted potential interactions between resveratrol and the five hub proteins, with the most favorable docking scores observed for TP53BP1 (- 7.0 kcal/mol) and DDX54 (- 6.9 kcal/mol). In vitro validation further showed that resveratrol treatment significantly reduced the mRNA and protein expression of the identified hub genes in A549 cells (P < 0.05). This study identified five lung cancer-associated hub genes and provided preliminary evidence that resveratrol may modulate their expression. These findings provide a multi-level molecular framework for further investigation of resveratrol-responsive networks in lung cancer.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"4495-4522"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758097","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}