Cell Biochemistry and Function最新文献

{"title":"Optogenetic Control of the Integrated Stress Response Limits Glioblastoma Invasion.","authors":"Lisa K Månsson, Ethan Dickson, Lun Hao, Angela A Pitenis, Maxwell Z Wilson","doi":"10.1002/cbf.70212","DOIUrl":"https://doi.org/10.1002/cbf.70212","url":null,"abstract":"<p><p>The integrated stress response (ISR) is a highly conserved signaling network, allowing cells to adapt and respond to various stressors. With its aggressive spread and high recurrence rates, glioblastoma multiforme (GBM) is one of the toughest cancers to date, yet the role of the ISR is still to be well understood, whether activation may suppress or promote this disease, and drug-treatment of GBM has thus far shown inconclusive results. In this work, we use an optogenetic tool, opto-PKR, to specifically trigger ISR activation via light-induced oligomerizing PKR-kinases, offering high spatiotemporal and reversible control, while avoiding potential upstream damage or side effects from drugs. Using immunofluorescence and RNA-sequencing, we show that targeted ISR activation reaching levels where both adaptive (ATF4) and terminal responses (CHOP) are activated results in subsequent downregulation of genes associated with the extracellular environment and glial cell migration, further supported by ECM-stain and scratch assays. Next, we show inhibition of aggressive spread for ISR-activated GBM spheroids in collagen 3D culture. Photopatterning of ISR activation in spheroids demonstrates a cell-intrinsic effect at the tissue scale, and recovery studies indicate a tunable, non-ablative intervention space. These findings suggest a route to containment and motivate ISR-activating small molecule screening in GBM models.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 4","pages":"e70212"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688605","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":"Hypercapnia-Regulated Molecular Pathways: Mechanistic Insights Into CO₂-Driven Cellular Signaling and Therapeutic Implications.","authors":"Mohammad-Taher Moradi, Sepideh Nouraei, Habibolah Khazaie, Amir Sharafkhaneh, Babak Mokhlesi","doi":"10.1002/cbf.70192","DOIUrl":"https://doi.org/10.1002/cbf.70192","url":null,"abstract":"<p><p>Long dismissed as a passive marker of ventilatory failure, elevated carbon dioxide (PaCO₂ > 45 mmHg) is now recognized as a potent signaling molecule that orchestrates complex cellular responses. This review synthesizes recent advances revealing how hypercapnia modulates fundamental processes, immune regulation, tissue repair, and metabolism, through direct molecular mechanisms. We detail how CO₂ triggers noncanonical NF-κB signaling, alters Wnt ligand secretion to impair alveolar regeneration, and exacerbates TLR4-primed NLRP3 inflammasome activation; this pro-inflammatory effect is most prominent in specific cell types like microglia and under conditions of sustained high CO₂ levels. Furthermore, hypercapnia drives profound metabolic reprogramming and induces lasting epigenetic changes, such as TET1-downregulation-mediated CDH1 hypermethylation, which reinforces immunosuppression in chronic lung disease. Critically, we evaluate emerging tools like CarboSen probes that enable more precise separation of CO₂-specific effects from associated acidosis in buffered experimental systems. Therapeutically, these insights argue for precision strategies: macrophage-specific Akt1 inhibition to restore antiviral immunity, localized Wnt agonists to promote repair, or targeting the leptin/STAT3/SOCS3 axis to improve ventilatory drive. However, translation requires navigating significant species differences and unresolved questions regarding epigenetic reversibility. By framing hypercapnia not as a uniform stressor but as a complex modulator whose effects are dictated by concentration, duration, and the specific tissue type involved, this review charts a course toward targeting CO₂-driven signaling for therapeutic benefit in conditions ranging from ARDS and COPD to obesity hypoventilation syndrome.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 4","pages":"e70192"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688607","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":"Targeting Cancer Signaling Pathways With Plant Sterols: Emerging Roles of Stigmasterol, Campesterol, and β-Sitosterol.","authors":"Suriyakanthan Menaga, Natesan Geetha","doi":"10.1002/cbf.70220","DOIUrl":"https://doi.org/10.1002/cbf.70220","url":null,"abstract":"<p><p>Plant sterols are naturally occurring tetracyclic triterpenes that serve as essential structural components of plant cell membranes. Structurally similar to cholesterol, these bioactive compounds have gained considerable attention for their diverse therapeutic properties, particularly their anticancer potential. Among them, stigmasterol, campesterol, and β-sitosterol are the most abundant and well-studied phytosterols known for their multifaceted roles in tumor suppression and apoptosis induction. They modulate several oncogenic signaling pathways, including PI3K/AKT/mTOR, JAK/STAT, NF-κB, and Wnt/β-catenin, thereby inhibiting cancer progression. Their anticancer activities involve mechanisms such as cell cycle arrest, activation of mitochondria-mediated apoptosis, inhibition of angiogenesis, and suppression of metastasis. Specifically, stigmasterol promotes apoptosis by upregulating Bax and p53, downregulating Bcl-2, and inhibiting angiogenic and JAK/STAT signaling. Campesterol induces cancer cell death through mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress, enhancing the efficacy of chemotherapeutic agents. β-sitosterol inhibits proliferation, triggers cell cycle arrest, regulates apoptotic proteins, and suppresses metastasis while overcoming drug resistance. Despite extensive individual studies, a comprehensive review summarizing their collective anticancer mechanisms is lacking. This work bridges that gap by systematically analyzing literature from the past 10 years across major databases, including Google Scholar, ScienceDirect, Scopus, Wiley Online Library, and Web of Science. Evidence from preclinical, clinical, and pharmacological studies was critically evaluated to highlight the therapeutic potential of these sterols in tumor suppression and apoptosis, providing a consolidated foundation for future drug discovery and development. The unique contribution of this review lies in proposing a comparative mechanistic framework for stigmasterol, campesterol, and β-sitosterol, integrating their multi-targeted actions across key oncogenic signaling pathways to highlight their collective potential in anticancer therapy.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 4","pages":"e70220"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762678","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":"Aporocactus flagelliformis Aqueous Extract Preserves Mitochondrial Integrity Under Glucose-Induced Oxidative Stress in 3T3-L1 Adipocytes.","authors":"Eun Hye Park, Sung-Jo Kim","doi":"10.1002/cbf.70217","DOIUrl":"https://doi.org/10.1002/cbf.70217","url":null,"abstract":"<p><p>Hyperglycemia-induced oxidative stress disrupts mitochondrial homeostasis in adipocytes. This study investigated the biochemical mechanisms by which Aporocactus flagelliformis aqueous extract (AFAE) preserves mitochondrial integrity under glucose overload, moving beyond its role as a simple antioxidant. GC-MS profiling identified an oxygen-rich phytochemical matrix, predominantly comprising malic acid (11.41%), citric acid (10.92%), and myo-inositol (8.74%). Molecular docking against aldose reductase (AKR1B1), a key enzyme in the polyol pathway, revealed a top-ranked binding affinity of -8.234 kcal/mol, forming hydrogen bonds with catalytic residues (TYR48, HIS110). Through methodologically rigorous, independent biological replicates (n ≥ 3) in 3T3-L1 adipocytes exposed to 50 mM glucose, AFAE (0.008-0.8 µg/mL) significantly reduced intracellular and mitochondrial reactive oxygen species, restored mitochondrial membrane potential (ΔΨₘ), and preserved organelle mass. These concurrent stabilizations indicate that AFAE mitigates upstream metabolic triggers potentially alleviating the \"NADPH steal\" phenomenon associated with excessive AKR1B1 flux rather than merely scavenging downstream ROS. Ultimately, this study provides a coherent preclinical foundation linking the phytochemical composition of AFAE to the modulation of the polyol-pathway-mitochondrial axis, underscoring its potential as a biochemical modulator of cellular redox homeostasis.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 4","pages":"e70217"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697461","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":"Synergistic Induction of Apoptosis by Apocytochrome C and Sodium Aescinate Is Mediated by Excessive Autophagy via the AKT-mTOR-TFEB Signaling Axis.","authors":"Jia-Wei Sun, Yin-Kang Chen, Liang Ji, Jian Zhao, Fu-Jun Wang","doi":"10.1002/cbf.70214","DOIUrl":"https://doi.org/10.1002/cbf.70214","url":null,"abstract":"<p><p>Cytochrome C (Cyt C) is a central mediator of intrinsic apoptosis, whereas its heme-free precursor, apocytochrome C (APO-Cyt C), competitively inhibits this process. Sodium aescinate (SA), a natural triterpene saponin, is known to facilitate the endosomal escape of protein drugs. We initially aimed to investigate the effects of enhancing endosomal escape efficiency on protein activity through the combination of SA and Cyt C. However, this study investigates an cytotoxicity observed when APO-Cyt C is combined with SA and aims to elucidate the underlying molecular mechanism. Contrary to its established anti-apoptotic function, APO-Cyt C, when co-administered with a non-toxic concentration of SA, induced potent, caspase-dependent mitochondrial apoptosis in cancer cells. This pro-apoptotic switch was not primarily triggered by BCL-2 family protein modulation, ROS generation, or calcium overload. Instead, the primary mechanism is the induction of excessive and lethal autophagy. SA was found to induce lysosomal membrane damage, evidenced by Galectin-9 recruitment, which initiates lysophagy. The addition of APO-Cyt C significantly amplified the autophagic flux, leading to decreased p62 levels and enhanced LC3-II turnover. Mechanistically, this synergy is driven by a dual impact on the AKT-mTOR-TFEB pathway: APO-Cyt C treatment decreased mTOR phosphorylation, while the combination promoted the nuclear translocation of the autophagy regulator, TFEB. Inhibition of autophagic flux using Bafilomycin A1 or Tetrandrine rescued cells from apoptosis, confirming that excessive autophagy is the direct cause of cell death. This study reveals a novel therapeutic strategy wherein an anti-apoptotic protein is converted into a potent pro-apoptotic agent. The combination of APO-Cyt C and SA triggers apoptosis by overwhelming the cell with excessive autophagic flux, driven by synergistic inhibition of the mTOR-TFEB axis. These findings highlight the therapeutic potential of modulating autophagy and suggest that combining mTOR inhibitors with lysosome-targeting agents like SA could be an effective anti-cancer strategy.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 4","pages":"e70214"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762752","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":"Melanocortin 3 Receptors Do Not Specifically Localize to Primary Cilia in Cultured Human and Rodent Neurons.","authors":"Niels Vos, Alessandro Moro, Wim Van Hul, Lotte Kleinendorst, Ralph J Florijn, Susanne E la Fleur, Matthijs Verhage, Mieke M van Haelst, Ruud F Toonen","doi":"10.1002/cbf.70216","DOIUrl":"10.1002/cbf.70216","url":null,"abstract":"<p><p>The melanocortin-3 receptor (MC3R) and the melanocortin-4 receptor (MC4R), both expressed in hypothalamic nuclei, are key downstream effectors of leptin signaling and play important roles in energy homeostasis. While pathogenic variants in the MC4R gene represent the most common cause of monogenic obesity, the clinical significance of MC3R variants is less clear. MC4R localizes to the primary cilium, a sensory organelle present on nearly all human cells. To better understand the pathophysiological mechanisms of MC3R variants, we investigated whether MC3R localizes to the primary cilium and assessed the impact of rare MC3R variants identified in individuals with obesity on ciliary expression. Using human RPE cells, human NGN2-induced iNeurons, and primary mouse hypothalamic neurons, we found that, in contrast to MC4R, neither wild type MC3R nor rare MC3R variants localized specifically to the primary cilium in vitro in any cell type, including hypothalamic neurons. These findings suggest that MC3R and MC4R may utilize distinct signaling pathways or that additional factors, such as accessory proteins, are required for MC3R targeting to primary cilia in vivo. Further studies are needed to clarify the role of MC3R variants in monogenic obesity and their broader implications for human disease.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 4","pages":"e70216"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MMP9 Serves as a Prognostic Biomarker and Immune-Associated Regulator in Diffuse Large B-Cell Lymphoma.","authors":"JunXiu Liu, JiaQi Qin, XiaoJing Shi, Qing Liu, XiaoCheng Cheng, Yue Zhou","doi":"10.1002/cbf.70200","DOIUrl":"https://doi.org/10.1002/cbf.70200","url":null,"abstract":"<p><p>Matrix metalloproteinase 9 (MMP9) is a zinc-dependent endopeptidase involved in extracellular matrix (ECM) remodeling and inflammatory signaling. Although MMP9 has been implicated in tumor progression and immune modulation in solid tumors, its clinical relevance and microenvironmental associations in diffuse large B-cell lymphoma (DLBCL) remain incompletely defined. Publicly available transcriptomic and clinical datasets of DLBCL were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GSE56315). Differential expression and enrichment analyses were performed to characterize biological pathways associated with MMP9 expression. Immune and stromal features were estimated using CIBERSORT, TIMER, and ESTIMATE algorithms. Associations with tumor stemness indices and somatic mutational profiles were explored. In addition, peripheral blood leukocyte profiles were analyzed from an independent cohort of DLBCL patients collected at our institution to assess systemic immune alterations associated with disease status. MMP9 protein expression was further evaluated using immunohistochemical data from the Human Protein Atlas. MMP9 expression was significantly elevated in DLBCL tissues compared with normal lymphoid controls. Higher MMP9 expression was associated with inferior overall survival and increased immune and stromal scores. MMP9 expression correlated with enhanced monocyte and myeloid cell infiltration and enrichment of ECM-related and cytokine-associated signaling pathways, including PI3K-Akt signaling. Analysis of peripheral blood samples revealed altered leukocyte distributions in DLBCL patients, characterized by increased neutrophil and monocyte proportions and reduced lymphocyte fractions, particularly in cases with bone marrow involvement. In addition, MMP9-high tumors exhibited distinct mutational patterns involving genes such as KMT2D and MYD88, along with reduced tumor stemness indices. Immunohistochemical analysis confirmed increased MMP9 protein expression in DLBCL tissues. Elevated MMP9 expression is associated with adverse prognosis and immune-stromal alterations in DLBCL. Integrated transcriptomic, genomic, and clinically derived peripheral blood analyses suggest that MMP9 expression reflects ECM-associated immune remodeling at both local and systemic levels, supporting its potential value as a biomarker linked to the tumor immune microenvironment in lymphoma.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 4","pages":"e70200"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688591","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":"Oxidative Stress and Inflammation in Methylmalonic and Propionic Acidemias: A Review.","authors":"Bianca Gomes Dos Reis, Ana Kalise Böttcher, Franciele Fátima Lopes, Debora Tonelotto, Luiza Wailer, Luísa Tedesco, Carmen Regla Vargas","doi":"10.1002/cbf.70219","DOIUrl":"https://doi.org/10.1002/cbf.70219","url":null,"abstract":"<p><p>Methylmalonic acidemia and propionic acidemia are inherited organic acidemias resulting from deficiencies in the enzymes methylmalonyl-CoA mutase and propionyl-CoA carboxylase, respectively. Impaired activity of these enzymes leads to the accumulation of propionyl-CoA and methylmalonyl-CoA metabolites in tissues and biological fluids. The two disorders share similar clinical features, most notably severe neurological involvement. In the absence of early diagnosis and appropriate treatment, affected individuals may develop irreversible neurological injury, progress to coma, and, in severe cases, death. In this scenario, this review presents some findings from studies in patients, cells and animal models, evidencing that oxidative stress and inflammation plays a crucial role in the pathophysiology of methylmalonic acidemia and propionic acidemia. Furthermore, it allows us to understand the profile of oxidative stress and new perspectives for the treatment of these diseases. Decreased antioxidant defenses, as well as increased levels of markers of inflammation, oxidative damage to lipids, proteins and DNA were observed in animal models, cells and patients, possibly due to the increase in the production of reactive species caused by the accumulated metabolites. The literature also indicates that the use of specific antioxidants may provide benefits by improving the oxidative profile. Based on this evidence, it is widely accepted that oxidative stress and inflammation contribute to severe neurological damage in patients with methylmalonic acidemia and propionic acidemia.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 4","pages":"e70219"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763545","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":"Significance of Lipid Metabolism Reprogramming in Tumor Microenvironment and Development of Novel Therapeutic Intervention.","authors":"Pallabi Mondal, Sankar Bhattacharyya","doi":"10.1002/cbf.70215","DOIUrl":"https://doi.org/10.1002/cbf.70215","url":null,"abstract":"<p><p>The metabolic reprogramming of cancer cell has recently gained heightened attention in the field of tumor metastasis. This metabolic reprogramming helps the cancer cells to meet increased energy and biosynthetic requirements. Beyond their structural role in membrane integrity, fatty aids are also crucial for the energy requirement of cancer cell which ultimately helps epithelial to mesenchymal transition and metastatic progression. There is urgent need for identifying the varied role of fatty acid metabolism in the tumor microenvironment (TME), that includes tumor cell, immune cells and stromal cells. Understanding how the tumor cells alter their lipid metabolism after their interaction with other cells in the TME can present a promising therapeutic strategy against cancer. This metabolic interaction between cancer cells and other cells of the TME (like immune cells and stromal cells) which supply fatty acids that helps in the formation of metastatic niche. In this review, we discussed in detail the role of exogenous fatty acid uptake and endogenous fatty acid synthesis in tumor cells and the mechanism through which cancer cells regulate lipid metabolism. Also, the involvement of immune and stromal cell in the metabolic reprogramming and the molecules or drugs that can affect the receptor or enzymes involved in lipid metabolism are identified. This review underscores the importance of further research focusing on targeting fatty acid metabolism to identify susceptibilities and enhance cancer therapy.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 4","pages":"e70215"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763533","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":"CircRNAs in Cutaneous Squamous Cell Carcinoma: Emerging Biomarkers and Potential Therapeutic Targets.","authors":"Jie Zou, Wenkang Qian, Jiangfeng Guo","doi":"10.1002/cbf.70218","DOIUrl":"https://doi.org/10.1002/cbf.70218","url":null,"abstract":"<p><p>The prevalence and invasiveness of cutaneous squamous cell carcinoma (cSCC), one of the most prevalent non-melanoma skin malignancies, are increasing annually. Effective biomarkers and targeted therapeutics for locally advanced, metastatic cSCC (i.e., tumors that are difficult to manage surgically due to extensive local invasion or distant spread) as well as for recurrent cSCC are still lacking, despite surgical resection being the primary therapy approach. Circular RNA (circRNA) has drawn a lot of interest lately in relation to cancer and development. There is evidence that circRNA can regulate biological processes like cell migration, invasion, and proliferation by acting as microRNA (miRNA) sponges. Furthermore, because of its tissue-specific expression, high stability, and wide range of regulatory roles, circRNA has demonstrated considerable relevance as a diagnostic marker and possible therapeutic target. This study provides a systematic review of the literature regarding the expression profiles of circRNAs in cSCC, the associated circRNA-miRNA-mRNA regulatory networks and molecular mechanisms, the involved signaling pathways, and their potential as therapeutic targets and diagnostic biomarkers. These findings may offer new approaches to the diagnosis, monitoring, and prognosis of cSCC.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 4","pages":"e70218"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721814","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}