Experimental cell research最新文献

{"title":"The role and mechanism of fatty acid-binding protein 7 in spinal reactive astrocytes in prolonged postoperative pain induced by high-fat diet","authors":"Han Zheng ,&nbsp;Xiao Zhang ,&nbsp;Mei Li ,&nbsp;Yu Wang ,&nbsp;Shufen Guo ,&nbsp;Ming Jiang ,&nbsp;Rui Xu ,&nbsp;Yulin Huang ,&nbsp;Zhengliang Ma","doi":"10.1016/j.yexcr.2025.114801","DOIUrl":"10.1016/j.yexcr.2025.114801","url":null,"abstract":"<div><div>Obesity markedly exacerbates nociceptive sensitivity and substantially compromises the quality of life of affected people. Astrocytes orchestrate metabolic regulation and homeostatic maintenance in the central nervous system. Notably, fatty acid binding protein 7 (FABP7) is highly expressed in astrocytes that governs intracellular fatty acid uptake and transport. While systemic hyperlipidemia is pathognomonic of obesity, the mechanistic contribution of FABP7 in astrocytes to obesity-associated pain pathophysiology remains poorly characterized. The present study established a model of high-fat diet (HFD)-induced obesity combined with a standardized hind paw surgical incision paradigm, aiming to unveil the role of astrocytic FABP7 in HFD-induced chronic pain. Furthermore, an <em>in vitro</em> high-fat environment was induced by palmitic acid (PA),aiming to investigate the molecular mechanisms by which primary astrocytes were activated into the A1 phenotype to mediate neuroinflammation. FABP7 was overexpressed in the spinal dorsal of HFD mice. The activation of A1-type astrocytes and neuroinflammation cascades involving elevated iNOS eventually resulted in mechanical allodynia in HFD mice. Pharmacological inhibition of FABP7 <em>via</em> an intraperitoneal administration of SBFI-26 (20 mg/kg) significantly attenuated the paw withdrawal mechanical threshold and inhibited the A1-type astrocytes activation. PA-induced high-fat conditions promoted lipid droplet accumulation and upregulated FABP7 in astrocytes. Pharmacological inhibition of FABP7 using SBFI-26 (100 μmol/L) significantly suppressed the neurotoxic C3-positive A1 astrocyte phenotype, reduced intracellular lipid droplet accumulation, thereby inhibiting the activation of A1-type astrocytes and alleviating neuroinflammation. Overall, FABP7-mediated astrocytic reprogramming was a critical nexus bridging obesity with chronic pain. A1-astrocyte polarization initiated neuroinflammatory amplification, forming a feedforward loop perpetuating central sensitization. Our findings are expected to offer a viable target for metabolic pain management.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114801"},"PeriodicalIF":3.5,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145388196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of everolimus on circadian gene expression and cell fate in synchronized Caco-2 cells","authors":"Dilek Ozturk Civelek ,&nbsp;Beyza Goncu ,&nbsp;Sadullah Goncu ,&nbsp;Alper Okyar","doi":"10.1016/j.yexcr.2025.114810","DOIUrl":"10.1016/j.yexcr.2025.114810","url":null,"abstract":"<div><h3>Objectives</h3><div>Circadian rhythms regulate key biological processes, including cell proliferation and metabolism, and their disruption is implicated in colorectal cancer (CRC). mTOR signaling interacts bidirectionally with the circadian clock, yet how mTOR inhibition modulates clock gene dynamics and cellular behavior in intestinal models remains unclear. This study aimed to investigate the effects of everolimus, an mTOR inhibitor, on circadian gene expression, cell viability, apoptosis, and cell cycle progression in synchronized Caco-2 cells, with consideration of cell confluency and Circadian Time (CT).</div></div><div><h3>Methods</h3><div>Caco-2 cells were synchronized using serum shock at 20 % and 70 % confluency. Time-series samples were collected across multiple CTs (CT6–CT60). Gene expression (<em>BMAL1, PER2, mTOR</em>) was assessed by qRT-PCR using <em>ACTB</em> and <em>RPLP0</em> as reference genes. Rhythmicity was evaluated via Cosinor analysis. Cell viability, apoptosis, and cell cycle dynamics were analyzed using the Muse™ Cell Analyzer following everolimus treatment (1–50 μM).</div></div><div><h3>Results</h3><div><em>RPLP0</em> proved to be a more stable reference gene than <em>ACTB</em>. <em>BMAL1</em> exhibited stronger rhythmic expression than <em>PER2</em>, particularly at 20 % confluency. Everolimus (50 μM) significantly reduced cell viability in a time-dependent manner, with the greatest effect at CT6 and CT18 (p &lt; 0.0001). Apoptosis was markedly increased at CT6 (+38.5 %) and moderate at CT18, indicating circadian modulation of drug sensitivity. Serum shock alone shifted cell cycle distribution, decreasing G0/G1 and increasing G2/M phase populations (p &lt; 0.01). Everolimus altered <em>BMAL1</em> and <em>PER2</em> expression rhythms and significantly reduced mTOR expression at CT30, where baseline mTOR levels were highest. Cosinor analysis confirmed rhythmicity in <em>BMAL1/RPLP0</em> and <em>mTOR/RPLP0</em> profiles under low confluency.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that everolimus influences circadian gene expression and exerts time-dependent antiproliferative and pro-apoptotic effects in Caco-2 cells. These results support the potential of circadian timing as a strategy to enhance mTOR-targeted therapies in CRC.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114810"},"PeriodicalIF":3.5,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145414066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EIF4A3-mediated localization of circDNAJC16 sequesters miR-93-5p to suppress lung adenocarcinoma progression via CDKN1A-regulated cell cycle and EMT","authors":"Liu Yang ,&nbsp;Yaodong Fan ,&nbsp;Yiyin Wang ,&nbsp;Chuntao Yan ,&nbsp;Zheng Guan ,&nbsp;Yuan Li ,&nbsp;Xiaosan Su ,&nbsp;Xiaowei Huang","doi":"10.1016/j.yexcr.2025.114799","DOIUrl":"10.1016/j.yexcr.2025.114799","url":null,"abstract":"<div><div>Lung adenocarcinoma (LUAD), the predominant non-small cell lung cancer subtype, exhibits high mortality due to metastasis and therapeutic resistance. While circular RNAs (circRNAs) are implicated in oncogenesis, their functional mechanisms and upstream regulation in LUAD remain incompletely characterized. This study identifies <strong>circDNAJC16 (hsa_circ_0000018)</strong> as significantly downregulated in advanced-stage LUAD (Stage III-IV vs. I-II, <em>p</em> = 0.001), where its low expression independently predicts poor survival (HR = 1.93, <em>p</em> = 0.043). Functional characterization demonstrates that circDNAJC16 overexpression suppresses <em>in vivo</em> tumor growth (volume reduction: 26.56 %, <em>p</em> &lt; 0.001) through cytoplasmic sequestration of <strong>oncogenic miR-93-5p</strong>, thereby activating <strong>CDKN1A/p21</strong> to induce G0/G1 cell cycle arrest and inhibit proliferation, while concurrently suppressing metastasis via epithelial-mesenchymal transition (EMT) regulation. Crucially, the RNA-binding protein <strong>eIF4A3</strong> binds upstream flanking introns of the host DNAJC16 pre-mRNA, driving selective nuclear retention of circDNAJC16 and redirecting linear DNAJC16 mRNA to the cytoplasm – a bifurcation mechanism essential for tumor suppression. These findings identify circDNAJC16 downregulation as a negative prognostic indicator in LUAD and reveal its dual tumor-suppressive roles: cytoplasmic sequestration of miR-93-5p activating CDKN1A-mediated cell cycle arrest, coupled with eIF4A3-governed nuclear retention controlling functional subcellular localization. Significantly, this work is the first to demonstrate eIF4A3-mediated circRNA compartmentalization, establishing circDNAJC16 as a novel prognostic biomarker and therapeutic target for LUAD.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114799"},"PeriodicalIF":3.5,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A tRNA-derived fragment tiRNA-Met-CAT-002 induced by myocardial ischemia/reperfusion injury inhibits cardiomyocyte autophagy by regulating Bnip3","authors":"Lang Deng ,&nbsp;Yawen Weng ,&nbsp;Jiahui Lin ,&nbsp;Lingfeng Zhong ,&nbsp;Zhixuan Tang ,&nbsp;Shuang Lin ,&nbsp;Weijian Huang ,&nbsp;Zhenfeng Cheng ,&nbsp;Kongjie Lu ,&nbsp;Bozhi Ye","doi":"10.1016/j.yexcr.2025.114809","DOIUrl":"10.1016/j.yexcr.2025.114809","url":null,"abstract":"<div><div>Myocardial ischemia/reperfusion (I/R) injury is a significant contributor to the development of heart failure. This study investigates the differential expression of tRNA-derived small RNAs (tsRNAs) during I/R and explores their potential functional implications. Through tRF &amp; tiRNA sequencing, we identified 115 tsRNAs exhibiting significant changes in expression following I/R. Notably, tiRNA-Met-CAT-002 was found to be upregulated via the hypoxia/hypoxia-inducible factor 1 subunit α (HIF1α)/angiogenin (ANG) signaling axis. Our findings suggest that Bnip3 represents a crucial target for tiRNA-Met-CAT-002. Mechanistically, mimics of tiRNA-Met-CAT-002 reduced Bnip3 protein expression by directly targeting the 3′ untranslated region (UTR) of its mRNA in a manner resembling microRNA activity. Furthermore, tiRNA-Met-CAT-002 was observed to decrease autophagy levels while enhancing cell viability under hypoxia/reoxygenation (H/R) conditions. In conclusion, this study underscores the substantial role of tsRNAs in the pathophysiology of I/R injury, with tiRNA-Met-CAT-002 potentially serving as a protective factor by attenuating autophagy levels.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114809"},"PeriodicalIF":3.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145360731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental delay in DCP2l(3)tb of Drosophila melanogaster is due to disruption in the regulation of ecdysone signaling","authors":"Govind R. Chaudhary,&nbsp;Vaishali Yadav,&nbsp;Jagat Kumar Roy","doi":"10.1016/j.yexcr.2025.114808","DOIUrl":"10.1016/j.yexcr.2025.114808","url":null,"abstract":"<div><div>The balance between mRNA synthesis and degradation plays an important role in gene regulation, their perturbation can lead to deleterious consequences to the cell. In eukaryotes, mRNA is degraded by a decapping protein-2 (DCP2). A hypomorph mutant allele of DCP2, <em>DCP2</em>^{<em>l(3)tb</em>}, identified in our lab, shows delayed moulting, pupariation and absolute lethality in pupal stages. In <em>Drosophila</em>, moulting and pupariation are primarily regulated by ecdysone which is modulated by a few regulators synthesized by the larval brain, some are stimulatory such as Prothoracicotropic hormone (PTTH) and <em>Drosophila</em> insulin-like peptides (Dilps); whereas some are inhibitory, such as Lgr3-expressing neurons. We aimed to investigate the cause of the delay in moulting and pupariation in <em>DCP2</em>^{<em>l(3)tb</em>} homozygous mutants. Through our RNA Seq data, we found downregulated expression of brain-derived neuropeptides such as <em>PTTH</em> and <em>Dilps</em> which were further confirmed and validated through qRT-PCR and semiquantitative PCR. Furthermore, we assessed the mRNA level of <em>Lgr3</em> which was found to be upregulated in the larval CNS of <em>DCP2</em>^{<em>l(3)tb</em>} homozygotes suggesting insufficient production of stimulatory modulators. Further, providing 20H-ecdysone exogenously through diet, curtailed the extended larval life. We propose that the larval CNS of <em>DCP2</em>^{<em>l(3)tb</em>} homozygotes produces insufficient brain-derived neuropeptides to stimulate the prothoracic gland to synthesize the ecdysone required for moulting and metamorphosis.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114808"},"PeriodicalIF":3.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of cuproptosis in osteoarthritis: Pathways, crosstalk, and therapeutic opportunities","authors":"Yanyang Shen ,&nbsp;Mingdong Liu ,&nbsp;Benson O.A. Botchway ,&nbsp;Yong Zhang ,&nbsp;Xuehong Liu","doi":"10.1016/j.yexcr.2025.114800","DOIUrl":"10.1016/j.yexcr.2025.114800","url":null,"abstract":"<div><div>Osteoarthritis (OA), the most prevalent degenerative joint disorder worldwide, continues to impose significant personal and societal burdens due to the absence of effective disease-modifying therapies. Recent advances in metallobiology have identified cuproptosis, a copper (Cu)-dependent regulated cell death pathway, as a potential driver of OA pathogenesis. In OA, dysregulated Cu homeostasis has been linked to oxidative stress, inflammatory signalling activation, mitochondrial dysfunction, and direct chondrocyte injury. Mechanistically, Cu²⁺ overload promotes aggregation of lipoylated tricarboxylic acid (TCA) cycle enzymes and destabilisation of iron–sulfur clusters, thereby impairing mitochondrial integrity and cellular metabolism. Emerging evidence also highlights extensive crosstalk between cuproptosis and ferroptosis, mediated largely by glutathione depletion and glutathione peroxidase 4 (GPX4) dysfunction, which amplifies oxidative damage in joint tissues. This review synthesises current evidence on Cu metabolism, the regulation and function of cuproptosis-related genes (CRGs), and their roles in immune infiltration, inflammatory signalling, and cartilage degeneration in OA. We further examine the interplay between cuproptosis and ferroptosis, and critically evaluate therapeutic strategies, including Cu chelation, antioxidant reinforcement, and pathway modulation, that may offer disease-modifying potential. By integrating these mechanistic insights, we aim to define new translational opportunities for OA management and outline priority areas for future research.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114800"},"PeriodicalIF":3.5,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to ‘Simvastatin inhibits the development of radioresistant esophageal cancer cells by increasing the radiosensitivity and reversing EMT process via the PTEN-PI3K/AKT pathway’ [Exp Cell Res. 2018 Jan 15;362(2):362–369]","authors":"Yingying Jin,&nbsp;Kun Xu,&nbsp;Qingjuan Chen,&nbsp;Baofeng Wang,&nbsp;Jiyuan Pan,&nbsp;Shan Huang,&nbsp;Yang Wei,&nbsp;Hongbing Ma","doi":"10.1016/j.yexcr.2025.114792","DOIUrl":"10.1016/j.yexcr.2025.114792","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 1","pages":"Article 114792"},"PeriodicalIF":3.5,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal protein restriction promotes cardiac disorders by disrupting heart developmental morphophysiology in young male offspring rats","authors":"Lucas Sobrinho Lemos ,&nbsp;Matheus Naia Fioretto ,&nbsp;Isabelle Tenori Ribeiro ,&nbsp;Luísa Annibal Barata ,&nbsp;Flávia Alessandra Maciel ,&nbsp;Felipe Leonardo Fagundes ,&nbsp;Renato Mattos ,&nbsp;Luiz Marcos Frediani Portela ,&nbsp;João Miguel Barboza ,&nbsp;Beatriz Souza de Oliveira ,&nbsp;Keila Emílio de Almeida ,&nbsp;Sérgio Alexandre Alcantara dos Santos ,&nbsp;Clélia Akiko Hiruma Lima ,&nbsp;José Ricardo de Arruda Miranda ,&nbsp;Elena Zambrano ,&nbsp;Luis Antonio Justulin","doi":"10.1016/j.yexcr.2025.114795","DOIUrl":"10.1016/j.yexcr.2025.114795","url":null,"abstract":"<div><div>In recent years, cardiovascular diseases have been one of the leading causes of death worldwide. Epidemiological and experimental studies have linked adverse intrauterine conditions with an susceptibility to cardiovascular and metabolic diseases in subsequent generations, a concept related to the Developmental Origins of Health and Disease (DOHaD). Here, we evaluated the maternal protein restriction (MPR), and its harmful effects on the cardiac morphophysiology of offspring in early life. During gestation and lactation, the pregnant rats were divided into two groups: Control (CTR), which received a normoprotein diet (17 % protein), and Gestational and Lactational Low-Protein (GLLP), which received a hypoprotein diet (6 % protein). At postnatal day 21, the offspring were euthanized. There was a decrease in serum levels of IGF1, an increase in testosterone, and a decrease in several phenotypic parameters in the heart, such as the size of cardiomyocytes and their nuclei, collagen, reticular and elastic fibers, and mast cells in the GLLP group. We observed that MPR led to electrical disorders in the heart (bradycardia), in addition to impacting angiogenic proteins (high Aquaporin1 and PECAM-1), and proteins associated with the antioxidant system (low Peroxiredoxin 4 and high GSTpi expressions) in the GLLP group. These adverse effects early in life increase the risk of pathophysiological remodeling of the heart, with the potential for hypertension, hypertrophy, and cardiovascular disease later in life.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 1","pages":"Article 114795"},"PeriodicalIF":3.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone marrow mesenchymal stem cell-derived exosomes HADH alleviate vitiligo by activating the Nrf2/HO-1 pathway","authors":"Shiyang Tang ,&nbsp;Xin Li ,&nbsp;Jianyuan Xi","doi":"10.1016/j.yexcr.2025.114798","DOIUrl":"10.1016/j.yexcr.2025.114798","url":null,"abstract":"<div><h3>Background</h3><div>Vitiligo is a chronic skin disorder that significantly impairs patients' quality of life. Exosomes (Exos) have been reported to hold therapeutic promise for vitiligo. This study aimed to investigate the molecular mechanism by which bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) ameliorate vitiligo.</div></div><div><h3>Methods</h3><div><em>In vitro</em> vitiligo cell model was established by hydrogen peroxide (H₂O₂)-induced melanocytes. A mouse model of vitiligo was also established. Immunofluorescence, cell counting kit-8, 2′,7′-dichlorofluorescein diacetate, enzyme linked immunosorbent assay, flow cytometry, real-time quantitative PCR, western blotting, hematoxylin-eosin, Masson-Fontana, and immunohistochemistry staining experiments were elucidated to explore the molecular mechanism of BMSC-Exos in relieving vitiligo.</div></div><div><h3>Results</h3><div>H₂O₂ treatment reduce the cell viability, superoxide dismutase and catalase activities, and promote reactive oxygen species production, pyroptosis, the expression of NLRP3, ASC, IL-1β and IL-18 proteins in melanocytes. BMSC-Exos treatment effectively counteracted these detrimental effects. Knockdown of exosomal HADH derived from BMSC enhanced H₂O₂-induced oxidative stress and pyroptosis in melanocytes. Mechanistically, BMSC-Exos attenuated H₂O₂-induced oxidative stress and pyroptosis by mediating HADH delivery to activate the Nrf2/HO-1 pathway. Moreover, these results were further confirmed by experiments in a mouse model of vitiligo.</div></div><div><h3>Conclusion</h3><div>BMSC-Exos can alleviate vitiligo by delivering HADH to activate the Nrf2/HO-1 pathway. This study provides insights for exploring new treatments for vitiligo.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114798"},"PeriodicalIF":3.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative multi-omics analysis identifies mitochondria- and ferroptosis-related prognostic genes in cervical cancer","authors":"Linlin Jia ,&nbsp;Xinyu Cui ,&nbsp;Xiaoting Li ,&nbsp;Rui Li","doi":"10.1016/j.yexcr.2025.114796","DOIUrl":"10.1016/j.yexcr.2025.114796","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondria and ferroptosis are crucial in tumorigenesis. However, their specific role in cervical cancer (CC) remains unclear. This study aimed to identify and validate prognostic genes linked to mitochondrial function and ferroptosis in CC.</div></div><div><h3>Methods</h3><div>Publicly available datasets were analyzed, including 306 CC tumor samples from The Cancer Genome Atlas-Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA-CESC), with survival data for 293 samples, a training set of 24 normal and 33 tumor tissues (GSE9750), and a validation set of 300 tumor tissues (GSE44001). Prognostic genes associated with mitochondria-related genes (MRGs) and ferroptosis-related genes (FRGs) were identified through machine learning, univariate Cox regression, Weighted Gene Co-expression Network Analysis (WGCNA), Mendelian randomization (MR), differential expression analysis, and multivariate Cox analysis. A risk model was constructed and validated, with the High-Risk Group (HRG) and Low-Risk Group (LRG) defined by optimal risk score thresholds. Independent prognostic analysis, functional enrichment, immune infiltration profiling, and single-cell resolution studies were conducted to explore the underlying molecular mechanisms. Additionally, gene expression was validated in five paired clinical samples (5 tumor/5 normal tissues) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).</div></div><div><h3>Results</h3><div>HSDL2, AMACR, and CBR3 were identified as prognostic genes. The risk model indicated significantly poorer survival rates in HRG patients (P &lt; 0.05). It demonstrated strong predictive performance, with area under the curve (AUC) values exceeding 0.7 in both the training and validation sets. The risk score, tumor (T) stage, and lymph node (N) stage were identified as independent prognostic factors for a nomogram model (hazard ratio (HR ≠ 1, P &lt; 0.5). Pathways co-enriched by these markers, such as allograft rejection, were investigated. Immune infiltration analysis revealed significant differences between HRG and LRG in M0 macrophages and resting myeloid dendritic cells (mDCs) (P &lt; 0.5). Macrophages and epithelial/cancer cells were identified as key contributors to CC progression, exhibiting 13 and 7 distinct differentiation states, respectively, in pseudo-time analysis. Notably, HSDL2 and CBR3 expression levels were significantly different between normal and CC samples (P &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>HSDL2, AMACR, and CBR3 were established as prognostic biomarkers for CC. The risk model demonstrated robust predictive accuracy, offering a scientific foundation for clinical prognosis prediction in CC.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114796"},"PeriodicalIF":3.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}