Pub Date : 2025-10-22DOI: 10.1016/j.yexcr.2025.114809
Lang Deng , Yawen Weng , Jiahui Lin , Lingfeng Zhong , Zhixuan Tang , Shuang Lin , Weijian Huang , Zhenfeng Cheng , Kongjie Lu , Bozhi Ye
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 & 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.
{"title":"A tRNA-derived fragment tiRNA-Met-CAT-002 induced by myocardial ischemia/reperfusion injury inhibits cardiomyocyte autophagy by regulating Bnip3","authors":"Lang Deng , Yawen Weng , Jiahui Lin , Lingfeng Zhong , Zhixuan Tang , Shuang Lin , Weijian Huang , Zhenfeng Cheng , Kongjie Lu , 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 & 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}
Pub Date : 2025-10-22DOI: 10.1016/j.yexcr.2025.114808
Govind R. Chaudhary, Vaishali Yadav, Jagat Kumar Roy
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, DCP2l(3)tb, identified in our lab, shows delayed moulting, pupariation and absolute lethality in pupal stages. In Drosophila, 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 Drosophila 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 DCP2l(3)tb homozygous mutants. Through our RNA Seq data, we found downregulated expression of brain-derived neuropeptides such as PTTH and Dilps which were further confirmed and validated through qRT-PCR and semiquantitative PCR. Furthermore, we assessed the mRNA level of Lgr3 which was found to be upregulated in the larval CNS of DCP2l(3)tb 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 DCP2l(3)tb homozygotes produces insufficient brain-derived neuropeptides to stimulate the prothoracic gland to synthesize the ecdysone required for moulting and metamorphosis.
{"title":"Developmental delay in DCP2l(3)tb of Drosophila melanogaster is due to disruption in the regulation of ecdysone signaling","authors":"Govind R. Chaudhary, Vaishali Yadav, 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><sup><em>l(3)tb</em></sup>, 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><sup><em>l(3)tb</em></sup> 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><sup><em>l(3)tb</em></sup> 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><sup><em>l(3)tb</em></sup> 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}
Pub Date : 2025-10-20DOI: 10.1016/j.yexcr.2025.114800
Yanyang Shen , Mingdong Liu , Benson O.A. Botchway , Yong Zhang , Xuehong Liu
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.
{"title":"Molecular mechanisms of cuproptosis in osteoarthritis: Pathways, crosstalk, and therapeutic opportunities","authors":"Yanyang Shen , Mingdong Liu , Benson O.A. Botchway , Yong Zhang , 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, Cu<sup>2+</sup> 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}
Pub Date : 2025-10-16DOI: 10.1016/j.yexcr.2025.114792
Yingying Jin, Kun Xu, Qingjuan Chen, Baofeng Wang, Jiyuan Pan, Shan Huang, Yang Wei, Hongbing Ma
{"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, Kun Xu, Qingjuan Chen, Baofeng Wang, Jiyuan Pan, Shan Huang, Yang Wei, 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}
Pub Date : 2025-10-15DOI: 10.1016/j.yexcr.2025.114795
Lucas Sobrinho Lemos , Matheus Naia Fioretto , Isabelle Tenori Ribeiro , Luísa Annibal Barata , Flávia Alessandra Maciel , Felipe Leonardo Fagundes , Renato Mattos , Luiz Marcos Frediani Portela , João Miguel Barboza , Beatriz Souza de Oliveira , Keila Emílio de Almeida , Sérgio Alexandre Alcantara dos Santos , Clélia Akiko Hiruma Lima , José Ricardo de Arruda Miranda , Elena Zambrano , Luis Antonio Justulin
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.
{"title":"Maternal protein restriction promotes cardiac disorders by disrupting heart developmental morphophysiology in young male offspring rats","authors":"Lucas Sobrinho Lemos , Matheus Naia Fioretto , Isabelle Tenori Ribeiro , Luísa Annibal Barata , Flávia Alessandra Maciel , Felipe Leonardo Fagundes , Renato Mattos , Luiz Marcos Frediani Portela , João Miguel Barboza , Beatriz Souza de Oliveira , Keila Emílio de Almeida , Sérgio Alexandre Alcantara dos Santos , Clélia Akiko Hiruma Lima , José Ricardo de Arruda Miranda , Elena Zambrano , 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}
Pub Date : 2025-10-15DOI: 10.1016/j.yexcr.2025.114798
Shiyang Tang , Xin Li , Jianyuan Xi
Background
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.
Methods
In vitro 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.
Results
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.
Conclusion
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.
{"title":"Bone marrow mesenchymal stem cell-derived exosomes HADH alleviate vitiligo by activating the Nrf2/HO-1 pathway","authors":"Shiyang Tang , Xin Li , 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 (H<sub>2</sub>O<sub>2</sub>)-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>H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub>-induced oxidative stress and pyroptosis in melanocytes. Mechanistically, BMSC-Exos attenuated H<sub>2</sub>O<sub>2</sub>-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}
Pub Date : 2025-10-15DOI: 10.1016/j.yexcr.2025.114796
Linlin Jia , Xinyu Cui , Xiaoting Li , Rui Li
Background
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.
Methods
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).
Results
HSDL2, AMACR, and CBR3 were identified as prognostic genes. The risk model indicated significantly poorer survival rates in HRG patients (P < 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 < 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 < 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 < 0.05).
Conclusion
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.
{"title":"Integrative multi-omics analysis identifies mitochondria- and ferroptosis-related prognostic genes in cervical cancer","authors":"Linlin Jia , Xinyu Cui , Xiaoting Li , 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 < 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 < 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 < 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 < 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}
Pub Date : 2025-10-14DOI: 10.1016/j.yexcr.2025.114797
Kai Li , Yaping Bai , Jingtong Wang , Li Ren , Anqi Mo , Haijun Liu , Wenjun Pei
Recent studies have highlighted the critical roles of long non-coding RNAs (lncRNAs) in tumorigenesis and progression. Here, we report that the lncRNA RNF216P1 is significantly upregulated in hepatocellular carcinoma (HCC) and contributes to tumor growth. To elucidate its underlying mechanisms, we first analyzed the transcriptional levels of RNF216P1 and its targets, miR-195-5p and autophagy related 4B cysteine peptidase (ATG4B), in HCC tissues using The Cancer Genome Atlas dataset, followed by validation with RT-qPCR. ATG4B protein levels were assessed by Western blotting. Functional assays—including xenograft models, CCK-8 viability tests, wound-healing assays, and Transwell migration assays—were performed to evaluate the role of RNF216P1 in HCC progression. Furthermore, the interactions between RNF216P1 and miR-195-5p, as well as between miR-195-5p and ATG4B, were confirmed by fluorescence in situ hybridization (FISH), RNA immunoprecipitation assays, and dual-luciferase reporter assays. Collectively, our findings demonstrate that RNF216P1 promotes malignant progression in HCC cells by acting as a competing endogenous RNA for miR-195-5p, thereby upregulating ATG4B and enhancing autophagy. This study identifies a novel ceRNA axis—RNF216P1/miR-195-5p/ATG4B—that plays a pivotal role in HCC development and may represent a potential therapeutic target.
{"title":"RNF216P1 functions as an oncogenic gene through modulating miR-195-5p/ATG4B axis in hepatocellular carcinoma","authors":"Kai Li , Yaping Bai , Jingtong Wang , Li Ren , Anqi Mo , Haijun Liu , Wenjun Pei","doi":"10.1016/j.yexcr.2025.114797","DOIUrl":"10.1016/j.yexcr.2025.114797","url":null,"abstract":"<div><div>Recent studies have highlighted the critical roles of long non-coding RNAs (lncRNAs) in tumorigenesis and progression. Here, we report that the lncRNA RNF216P1 is significantly upregulated in hepatocellular carcinoma (HCC) and contributes to tumor growth. To elucidate its underlying mechanisms, we first analyzed the transcriptional levels of RNF216P1 and its targets, miR-195-5p and autophagy related 4B cysteine peptidase (ATG4B), in HCC tissues using The Cancer Genome Atlas dataset, followed by validation with RT-qPCR. ATG4B protein levels were assessed by Western blotting. Functional assays—including xenograft models, CCK-8 viability tests, wound-healing assays, and Transwell migration assays—were performed to evaluate the role of RNF216P1 in HCC progression. Furthermore, the interactions between RNF216P1 and miR-195-5p, as well as between miR-195-5p and ATG4B, were confirmed by fluorescence in situ hybridization (FISH), RNA immunoprecipitation assays, and dual-luciferase reporter assays. Collectively, our findings demonstrate that RNF216P1 promotes malignant progression in HCC cells by acting as a competing endogenous RNA for miR-195-5p, thereby upregulating ATG4B and enhancing autophagy. This study identifies a novel ceRNA axis—RNF216P1/miR-195-5p/ATG4B—that plays a pivotal role in HCC development and may represent a potential therapeutic target.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 1","pages":"Article 114797"},"PeriodicalIF":3.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307250","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}
Pub Date : 2025-10-13DOI: 10.1016/j.yexcr.2025.114794
Zhigang Pan , Chuhan Ke , Bojun Zhang , Qingxin Lin , Hanlin Zheng , Shuni Zheng , Jinzhong Huang , Weipeng Hu
Gliomas, particularly high-grade glioblastomas, are highly aggressive malignancies with limited treatment options and poor prognosis. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising therapeutic target in cancer. However, the mechanisms regulating ferroptosis in glioma remain poorly understood. In this study, we identify FERMT1 as a key suppressor of ferroptosis in glioma cells. Using gain and loss-of-function experiments, we demonstrate that FERMT1 overexpression protects glioma cells from erastin-induced ferroptosis, while FERMT1 deficiency sensitizes cells to ferroptotic cell death. Treatment with the ferroptosis inhibitor ferrostatin-1 mitigates the effects of FERMT1 deficiency, underscoring the importance of ferroptosis suppression in FERMT1-mediated oncogenesis. Mechanistically, FERMT1 interacts with MBOAT2 to suppress ferroptosis. Depletion of MBOAT2 abolishes the anti-ferroptotic effects of FERMT1, whereas MBOAT2 overexpression rescues ferroptosis in FERMT1-deficient cells. Collectively, our findings reveal a previously unrecognized FERMT1-MBOAT2 axis that regulates ferroptosis in glioma cells and provide new insights into the molecular mechanisms underlying glioma progression. Targeting this axis may offer a novel therapeutic strategy for inducing ferroptosis and improving treatment outcomes in glioma.
{"title":"FERMT1 suppresses the ferroptosis of glioma cells by interacting with MBOAT2","authors":"Zhigang Pan , Chuhan Ke , Bojun Zhang , Qingxin Lin , Hanlin Zheng , Shuni Zheng , Jinzhong Huang , Weipeng Hu","doi":"10.1016/j.yexcr.2025.114794","DOIUrl":"10.1016/j.yexcr.2025.114794","url":null,"abstract":"<div><div>Gliomas, particularly high-grade glioblastomas, are highly aggressive malignancies with limited treatment options and poor prognosis. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising therapeutic target in cancer. However, the mechanisms regulating ferroptosis in glioma remain poorly understood. In this study, we identify FERMT1 as a key suppressor of ferroptosis in glioma cells. Using gain and loss-of-function experiments, we demonstrate that FERMT1 overexpression protects glioma cells from erastin-induced ferroptosis, while FERMT1 deficiency sensitizes cells to ferroptotic cell death. Treatment with the ferroptosis inhibitor ferrostatin-1 mitigates the effects of FERMT1 deficiency, underscoring the importance of ferroptosis suppression in FERMT1-mediated oncogenesis. Mechanistically, FERMT1 interacts with MBOAT2 to suppress ferroptosis. Depletion of MBOAT2 abolishes the anti-ferroptotic effects of FERMT1, whereas MBOAT2 overexpression rescues ferroptosis in FERMT1-deficient cells. Collectively, our findings reveal a previously unrecognized FERMT1-MBOAT2 axis that regulates ferroptosis in glioma cells and provide new insights into the molecular mechanisms underlying glioma progression. Targeting this axis may offer a novel therapeutic strategy for inducing ferroptosis and improving treatment outcomes in glioma.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114794"},"PeriodicalIF":3.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299451","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}
Pub Date : 2025-10-13DOI: 10.1016/j.yexcr.2025.114793
Jana Durackova , Ramya Potabattula , Andreas Rosenwald , Thomas Haaf
The absolute number of rDNA transcription units (TU) can vary by about one order of ten among individuals. Apart from extensive rDNA copy number (CN) variation and instability in many cancers, there is little information on the extent of intraindividual CN variation between normal tissues. Here we used droplet digital PCR and deep bisulfite sequencing to determine both the absolute rDNA CN and the number of presumably active CN with a hypomethylated (≤10 %) promoter region in up to six different tissues of 13 autopsy probands. In general, the absolute rDNA CN as well as the frequency of the minor A variant were highly similar between tissues (cerebellum, cerebrum, colon, heart, intestine, kidney, liver, and spleen) of the same individual. However, in some probands absolute CN in one or multiple tissues was much higher than in the other tissues, indicative of relaxation/breakdown of the CN control system. The amplified copies were inactivated by promoter methylation and, thus, the number of active CN was largely independent from absolute CN. Collectively, our data suggest that with some notable exceptions absolute and even more active rDNA CN are maintained during development and differentiation in different tissues of the same individual. Despite the low intraindividual variation active CN appeared to systematically vary between tissues. Cerebellum and cerebrum consistently exhibited lower active CN than the other analyzed tissues. We estimate that >50 active rDNA TU are required for normal tissue/organ function.
{"title":"Intraindividual rDNA copy number variation and methylation in humans","authors":"Jana Durackova , Ramya Potabattula , Andreas Rosenwald , Thomas Haaf","doi":"10.1016/j.yexcr.2025.114793","DOIUrl":"10.1016/j.yexcr.2025.114793","url":null,"abstract":"<div><div>The absolute number of rDNA transcription units (TU) can vary by about one order of ten among individuals. Apart from extensive rDNA copy number (CN) variation and instability in many cancers, there is little information on the extent of intraindividual CN variation between normal tissues. Here we used droplet digital PCR and deep bisulfite sequencing to determine both the absolute rDNA CN and the number of presumably active CN with a hypomethylated (≤10 %) promoter region in up to six different tissues of 13 autopsy probands. In general, the absolute rDNA CN as well as the frequency of the minor A variant were highly similar between tissues (cerebellum, cerebrum, colon, heart, intestine, kidney, liver, and spleen) of the same individual. However, in some probands absolute CN in one or multiple tissues was much higher than in the other tissues, indicative of relaxation/breakdown of the CN control system. The amplified copies were inactivated by promoter methylation and, thus, the number of active CN was largely independent from absolute CN. Collectively, our data suggest that with some notable exceptions absolute and even more active rDNA CN are maintained during development and differentiation in different tissues of the same individual. Despite the low intraindividual variation active CN appeared to systematically vary between tissues. Cerebellum and cerebrum consistently exhibited lower active CN than the other analyzed tissues. We estimate that >50 active rDNA TU are required for normal tissue/organ function.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"453 2","pages":"Article 114793"},"PeriodicalIF":3.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299428","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号