International journal of molecular medicine最新文献

{"title":"CENPU promotes tumorigenesis and stem cell properties in triple‑negative breast cancer by suppressing lysosomal furin degradation.","authors":"Shujuan Sun, Zhenyu Hou, Ling Qiang, Dongdong Zhou","doi":"10.3892/ijmm.2025.5649","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5649","url":null,"abstract":"<p><p>Centromere protein U (CENPU), a critical component of the kinetochore complex, structurally integrates with spindle microtubules to mediate chromosome segregation during mitosis. However, the association between CENPU expression levels and tumors is largely unknown. Immunohistochemistry and western blotting were used to analyze CENPU expression and prognostic value in breast cancer tissues. CENPU overexpressing/knockdown cell lines were constructed for 4D‑data‑independent acquisition quantitative proteomics and enrichment analyses. Functional assays, including flow cytometry, mammosphere formation, wound healing and Transwell assay, were used to assess the effects of CENPU on breast cancer stemness, migration and invasion. The associations among CENPU, nerve growth factor (NGF), proNGF and furin were also explored through western blotting, co‑immunoprecipitation and ELISA experiments. Finally, xenograft mouse models were established to verify the <i>in vivo</i> effects of CENPU on tumorigenesis and the inhibitory effect of furin inhibitor on CENPU‑promoted tumor growth. In the present study, immunohistochemistry and western blotting assessment of human breast cancer tissue specimens revealed a positive association between CENPU expression and the degree of invasiveness. The aforementioned functional analyses demonstrated that CENPU promoted stem cell‑like behavior and tumorigenicity, and induced malignancy in BC cells. Mechanistically, western blotting analysis demonstrated that CENPU promoted furin activity by inhibiting its lysosomal degradation. Furin, which is a precursor‑processing enzyme of (NGF), promoted the conversion of NGF precursor to NGF, which could promote BC stem cell properties in triple‑negative BC (TNBC). A tumorigenesis assay conducted in xenograft mouse models showed that CENPU promoted tumorigenesis, and treatment with a furin inhibitor suppressed this effect. The findings of the present study revealed that CENPU serves a critical role in furin‑mediated signaling responsible for tumorigenesis. Therefore, CENPU may be a novel molecular target in TNBC.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cynarin as a potent anti‑osteolytic agent: Targeting MAPK and Nrf2‑Keap1 pathways for osteoclast inhibition and bone protection.","authors":"Rui Chao, Yexin Wang, Zhan Liu, Tianhao Wan, Yi Mao, Xinru Xie, Lei Sun, Weifeng Xu, Xuzhuo Chen, Shanyong Zhang","doi":"10.3892/ijmm.2025.5647","DOIUrl":"10.3892/ijmm.2025.5647","url":null,"abstract":"<p><p>Inflammatory bone resorption, especially bone loss caused by the abnormal activation of osteoclasts (OCs), has become an increasing health concern. As a natural anti‑inflammatory compound, cynarin has shown potential in the treatment of various inflammatory diseases; however, its role in inflammatory bone resorption remains to be investigated. The present study aimed to explore the therapeutic potential of cynarin in inflammatory bone resorption by focusing on its regulatory effects on OC differentiation, inflammatory responses and related signalling pathways. Our results showed that cynarin significantly inhibited bone resorption, reduced tartrate‑resistant acid phosphatase activity, and downregulated key OC differentiation markers (<i>Atp6v0d2</i>, <i>Nfatc1</i>, <i>Dcstamp</i> and <i>Ctsk</i>). RNA sequencing and western blot analyses revealed that cynarin inhibited mitogen‑activated protein kinase (MAPK) pathway activation, and that the MAPK‑specific activator anisomycin reversed this inhibitory effect. In addition, cynarin alleviated the inflammatory response by reducing reactive oxygen species levels and inhibiting the expression of inflammatory cytokines. More importantly, cynarin activated Nrf2 and enhanced the expression of antioxidant genes (<i>Hmox</i> and <i>Cat</i>). Micro‑computed tomography analysis revealed that cynarin significantly enhanced the bone structure in mice, as indicated by increased bone volume and trabecular number, and trabecular thickness. Histological analysis confirmed that cynarin inhibited the expression of OC markers (tartrate‑resistant acid phosphatase, receptor activator of nuclear factor κB and cathepsin K) and inflammatory factors (tumor necrosis factor‑alpha and inducible nitric oxide synthase), while promoting osteogenic markers (osteocalcin and RUNX2). Finally, cynarin‑treated mice showed enhanced Nrf2 nuclear translocation and inhibition of MAPK signalling. These findings revealed the multiple roles of cynarin in the treatment of inflammatory osteolysis and provided insights into its potential therapeutic mechanisms and targets.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calycosin attenuates mitochondrial damage and pyroptosis in heart failure via the Nrf2/ROS/TXNIP pathway.","authors":"Hua-Jing Yuan, Quan-Cheng Han, Yi-Ding Yu, Hui Yu, Xiu-Juan Liu, Yi-Tao Xue, Yan Li","doi":"10.3892/ijmm.2025.5653","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5653","url":null,"abstract":"<p><p>Heart failure (HF) is a key public health concern worldwide due to its high morbidity and mortality rates. Calycosin (CA) is a flavonoid natural product that effectively treats HF with cardioprotective effects; however, its mechanism of action remains unclear. The present study aimed to investigate the therapeutic effect of CA on HF and its mechanism through <i>in vivo</i> and <i>in vitro</i> experiments, and to reveal the roles of pyroptosis and mitochondrial dysfunction in the pathophysiology of HF. The HF model was constructed 4 weeks after ligation of the left anterior descending artery in rats. Myocardial ischemia‑reperfusion injury was simulated using a hypoxia‑reoxygenation model and nuclear factor erythroid 2‑related factor (Nrf2) was silenced by transfection using small interfering RNA to further explore the therapeutic mechanism of CA. The results revealed that CA treatment improved cardiac function and myocardial injury, suppressed oxidative stress levels and improved mitochondrial ultrastructure in HF‑induced rats. CA downregulated the expression of relevant pyroptosis proteins via the Nrf2/reactive oxygen species (ROS)/thioredoxin‑interacting protein (TXNIP) pathway. <i>In vitro</i> experiments demonstrated consistent results confirming that CA ameliorated mitochondrial damage by reducing levels of ROS and inhibiting mitochondrial gasdermin D N‑terminal fragments activation. Silencing Nrf2 partially reversed the cardioprotective effects of CA, confirming the key therapeutic role of CA in Nrf2‑mediated anti‑pyroptosis. In conclusion, CA inhibits pyroptosis and improves mitochondrial damage in HF through the Nrf2/ROS/TXNIP pathway, which may disrupt the crosstalk between mitochondrial damage and pyroptosis, thereby exerting cardioprotective effects.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity in reproduction: Mechanisms from fertilization to post‑uterine development (Review).","authors":"Nikola Pavlović, Marinela Križanac, Marko Kumrić, Katarina Vukojević, Doris Rušić, Joško Božić","doi":"10.3892/ijmm.2025.5645","DOIUrl":"10.3892/ijmm.2025.5645","url":null,"abstract":"<p><p>Obesity, a global health concern defined by excessive adiposity and persistent metabolic imbalance, has far‑reaching implications that extend beyond standard metabolic and cardiovascular comorbidities. While the association between obesity and reproductive dysfunction is well‑established, the precise molecular mechanisms underlying these associations remain incompletely understood, particularly as regards the distinction between obesity‑specific effects and those mediated by dietary components or metabolic syndrome. The present review integrates currently available knowledge on the mechanisms through which obesity impairs reproductive function in both sexes, from gametogenesis to postnatal development. In males, obesity drives testicular inflammation, disrupts spermatogenesis, impairs sperm motility and DNA integrity, and alters key signaling pathways, with oxidative stress and metabolic endotoxemia as central mediators. In females, obesity induces ovarian dysfunction, alters steroidogenesis, compromises oocyte quality and disrupts follicular environments, leading to reduced fertility and adverse pregnancy outcomes. However, the relative contribution of obesity‑induced inflammation vs. direct lipotoxic effects remains poorly characterized in both sexes. The present review further examines the impact of parental obesity on fertilization capacity, placental function and in utero development, highlighting sex‑specific and intergenerational effects mediated by mitochondrial dysfunction and epigenetic modifications. Notably, maternal obesity impairs placental and fetal organ development, increases the risk of metabolic and reproductive disorders in offspring, and alters key developmental signaling pathways. While some studies suggest that lifestyle interventions and antioxidant therapies may partially reverse obesity‑induced reproductive impairments, significant gaps remain in understanding the precise molecular mechanisms and potential for therapeutic rescue. By synthesizing findings from animal models and human studies, the present review highlights the pivotal role of oxidative stress as a mechanistic link between obesity and reproductive dysfunction. It emphasizes the need for further research to inform clinical strategies aimed at mitigating these adverse outcomes.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterophyllin B enhances the benefits of intermittent fasting in the treatment of metabolic dysfunction‑associated steatotic liver disease via activation of GLP‑1R.","authors":"Kaimin Li, Ligong Deng, Lijun Xue, Shukun Yao","doi":"10.3892/ijmm.2025.5641","DOIUrl":"10.3892/ijmm.2025.5641","url":null,"abstract":"<p><p>Intermittent fasting (IF) has shown particularly promising short‑term effects in improving metabolic dysfunction‑associated steatotic liver disease (MASLD), although its long‑term efficacy remains unclear. Heterophyllin B (HP‑B), a cyclopeptide compound derived from <i>Pseudostellaria heterophylla</i>, is known for its potent anti‑inflammatory and hypoglycemic properties. However, studies investigating the potential role of HP‑B in the management of MASLD are lacking. In vitro, an OA/PA‑induced lipid accumulation model was established using HepG2/Huh‑7 cells. The therapeutic effects of HP‑B and fasting‑mimicking conditions were evaluated through Cell Counting Kit‑8 assay, Oil Red O staining, reverse transcription‑quantitative PCR, and western blot analysis. For <i>in vivo</i> studies, C57BL/6J mice were fed a high‑fat diet and treated with HP‑B, IF, or their combination. Mechanistic validation was performed via adenovirus‑mediated GLP‑1R knockdown. The present study aimed to explore whether HP‑B can serve as an adjunctive supplement to enhance the benefits of IF in the treatment of MASLD. HepG2 and Huh‑7 liver cancer cells treated with oleic acid/palmitic acid (OA/PA) presented significant lipid accumulation, which was attenuated by HP‑B treatment and fasting. The combination treatment markedly reduced lipid levels and oxidative stress, as well as restored the mitochondrial membrane potential, with a synergistic effect over treatment alone. In addition, the combination of HP‑B and fasting upregulated glucagon‑like peptide‑1 receptor (GLP‑1R) and peroxisome proliferator‑activated receptor gamma coactivator 1‑alpha expression, reversing the OA/PA‑induced decline. In high‑fat diet‑fed mice, the combination treatment reduced hepatic lipid accumulation, decreased liver weight, decreased mouse body weight, and improved biochemical indices of liver function. The beneficial effects of HP‑B and fasting were reversed after silencing GLP‑1R with small interfering RNA or Ad‑GLP‑1R, emphasizing the critical role of GLP‑1R in mediating these protective effects. In conclusion, the synergistic effects of HP‑B and fasting on improving lipid metabolism and mitochondrial function are mediated primarily through the regulation of GLP‑1R, making it a promising therapeutic target for the treatment of MASLD and other lipid metabolism‑related disorders.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of action of retinal microglia in diabetic retinopathy (Review).","authors":"Yuyang Bai, Xinrong Wang, Fan Qi, Xiaoyang Zuo, Gang Zou","doi":"10.3892/ijmm.2025.5643","DOIUrl":"10.3892/ijmm.2025.5643","url":null,"abstract":"<p><p>Diabetic retinopathy (DR), a leading cause of blindness in diabetic microvascular complications, is pathologically associated with the dynamic regulation of retinal microglia. The present review systematically elucidated the dual roles of microglia in DR pathogenesis. Under physiological conditions, microglia maintain blood‑retinal barrier (BRB) integrity by phagocytosing metabolic debris and secreting neurotrophic factors. However, hyperglycaemic stress induces pathological M1 polarization, triggering a cytokine storm (TNF‑α and IL‑1β) via the Toll‑like receptor 4/myeloid differentiation primary response 88/NF‑κB signalling axis, which synergizes with proangiogenic factors (such as VEGF and insulin‑like growth factor 1) to exacerbate BRB breakdown and pathological neovascularization. Notably, activated microglia amplify inflammatory cascades through astrocyte‑Müller cell interaction networks, accelerating neurovascular unit dysfunction. Emerging therapeutic strategies targeting microglial polarization homeostasis (such as promoting M2 anti‑inflammatory phenotypic shifts) and blocking critical inflammatory signalling pathways present novel opportunities for developing multitarget therapeutic agents with combined neuroprotective and anti‑vasopermeability properties. By elucidating microglial heterogeneity and intercellular regulatory networks, the present review highlighted the importance of precise modulation of immune homeostasis in DR management, providing a theoretical foundation for overcoming the limitations of single‑target therapies.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The gut‑skin axis: Emerging insights in understanding and treating skin diseases through gut microbiome modulation (Review).","authors":"Yuantong Zhao, Chenchen Yu, Jingyu Zhang, Qinghua Yao, Xiao Zhu, Xiaorong Zhou","doi":"10.3892/ijmm.2025.5651","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5651","url":null,"abstract":"<p><p> Emerging evidence indicates a significant association between the composition and functionality of the gut microbiome and various skin disorders, including psoriasis, atopic dermatitis, acne and several dermatological conditions. The gut‑skin axis theory describes a complex bidirectional communication network between the gut and the skin, providing mechanistic insights into the pathogenesis of certain cutaneous diseases. Specifically, the gut microbiome influences skin health through the regulation of systemic immunity, inflammatory responses and metabolic pathways. Advances in high‑throughput sequencing and bioinformatics technologies have substantially enhanced the understanding of the role of the gut microbiome in skin pathology. Clinical and preclinical studies have demonstrated that restoring gut microbial homeostasis via interventions such as faecal microbiota transplantation, probiotics and prebiotics can ameliorate symptoms of skin diseases. Furthermore, personalized microbiome‑based therapies, next‑generation probiotics and dietary modifications hold promise for refining gut‑skin interactions and advancing precision medicine in dermatology. Therapeutic strategies targeting the gut‑skin axis offer novel avenues for innovative dermatological treatments, with future breakthroughs potentially involving microbial community engineering, postbiotics and artificial intelligence in microbiome‑related diagnostics. This narrative review summarizes recent advances in gut‑skin axis research, explores its potential in the prevention and management of selected dermatoses and discusses future trends and scientific developments in the field.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial dysfunction in perimenopausal mood disorders: From hormonal shifts to neuroenergetic failure (Review).","authors":"Yang Yu, Han Yapeng, Zelin Liu, Lei Fang, Jianuo Li, Yifeng Luan, Wenzhong Li, Huifang Cong, Xiuhong Wu","doi":"10.3892/ijmm.2025.5656","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5656","url":null,"abstract":"<p><p>Perimenopause represents a key transition from a reproductive to non‑reproductive state in women, characterized by physiological and psychological changes. Mood disturbances during this period, such as depression, anxiety and cognitive decline, are increasingly understood as complex neuroendocrine and metabolic disorders. Mitochondrial homeostasis carries out a key role in the pathophysiology of these affective symptoms. Disruptions in mitochondrial biogenesis, mitophagy and calcium regulation contribute to synaptic dysfunction and neuroimmune changes. These mitochondrial alterations interact with inflammatory pathways and hormonal signals, exacerbating neuropsychiatric symptoms. A more comprehensive understanding of the molecular mechanisms of mitochondrial dysfunction in menopausal mood disorders unveils potential therapeutic strategies, including mitochondria‑targeted antioxidants, hormone replacement therapy, and lifestyle interventions designed to restore mitochondrial integrity and cerebral bioenergetic function.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in the endoplasmic reticulum‑mitochondria communication in dermal fibroblasts from early‑stage bipolar disorder patients: Skin‑brain axis as a new route to understand the pathophysiology of mental illness?","authors":"Ana Catarina Pereira, Ana Patrícia Marques, Rosa Resende, Laura Serrano-Cuñarro, Margarida Caldeira, Tânia Fernandes, Mariana Batista, António Macedo, Joana Barbosa De Melo, Nuno Madeira, Cláudia Cavadas, Maria Teresa Cruz, Cláudia Fragão Pereira","doi":"10.3892/ijmm.2025.5654","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5654","url":null,"abstract":"<p><p>Compromised cellular resilience in bipolar disorder (BD) has been associated with structural brain changes and cognitive deficits caused by perturbation of redox status, endoplasmic reticulum (ER) stress and innate immunity. These crucial cellular events are regulated by the ER‑mitochondria close contacts at mitochondria‑associated membranes (MAM) through Ca²⁺ transfer and lipids exchange between these organelles. The present study aimed to investigate the structural and functional alterations in MAM during BD early stages using patient‑ and control‑derived cellular models, namely dermal fibroblasts. Morphological alterations in close ER‑mitochondria contacts at MAM occur in BD cells and correlate with functional changes, as shown by lipid droplets accumulation. The MAM dysfunction in BD cells parallels changes in Ca²⁺ homeostasis, namely inhibition of store‑operated Ca²⁺ entry (SOCE), ER Ca²⁺ depletion and attenuation of ER‑mitochondria Ca²⁺ transfer, as well as enhanced ER and oxidative stress and NOD‑like receptor family pyrin domain‑containing 3 (NLRP3) inflammasome activation leading to sterile inflammation. The absence of inflammasome activation upon lipopolysaccharide exposure supports the compromised ability of BD cells (fibroblasts as well as monocytes) to deal with stressful conditions. In conclusion, MAM disruption is highlighted as a potential pathophysiological mechanism driving impaired cellular resilience in BD. Skin fibroblasts are a particularly attractive cellular model for studying mental illnesses, such as BD, due to the shared developmental origin of epidermal and neural tissues. The ectodermal origins of the skin‑brain axis have been proposed as a novel route for understanding brain development, neurodevelopmental conditions and behavior modulation.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging role of long non‑coding RNAs in the Rho/ROCK signaling pathway in tumor metastasis (Review).","authors":"Hui Nie, Xuejie Yang, Qingning Chen, Xiaoyun He, Yingying Han, Qiuyan He, Chunlin Ou","doi":"10.3892/ijmm.2025.5638","DOIUrl":"10.3892/ijmm.2025.5638","url":null,"abstract":"<p><p>Metastasis is a critical feature of malignant tumors and a major cause of treatment failure and poor prognosis. This complex process primarily involves the rearrangement of the cytoskeleton. Among several cytoskeleton‑associated signaling pathways, the ras homolog family (Rho) and Rho‑associated coiled‑coil containing protein kinase (ROCK) signaling pathway serves a key role in cytoskeleton regulation as it controls intracellular actin dynamics and cytoskeletal remodeling to mediate cell movement. Long non‑coding RNAs (lncRNAs), known to serve important roles in tumorigenesis and metastasis, have been shown to regulate the Rho/ROCK pathway. lncRNAs modulate the Rho/ROCK pathway by sponging microRNAs or directly binding to proteins, thereby mediating tumor metastasis. Additionally, lncRNAs can be encapsulated in exosomes and transferred from donor cells to recipient cells, where they regulate components of the Rho/ROCK signaling pathway and further promote the metastatic potential. Based on their functional significance, Rho/ROCK signaling pathway‑associated lncRNAs may serve as novel tumor biomarkers and therapeutic targets. The present review summarizes the role and mechanism of Rho/ROCK signaling pathway‑associated lncRNAs in tumor metastasis, which may offer novel avenues for the diagnosis and treatment of metastatic cancer.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}