Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Molecular Alterations in Ferroptosis and the Effects of Resveratrol: A Systematic Review","authors":"Ana Beatriz Dos Santos,&nbsp;Júlio Santos-Terra,&nbsp;Jaqueline Vieira Carletti,&nbsp;Iohanna Deckmann,&nbsp;Carmem Gottfried","doi":"10.1002/jbt.70384","DOIUrl":"https://doi.org/10.1002/jbt.70384","url":null,"abstract":"<p>Ferroptosis is an iron-dependent cell death. Different from other types of cell death, ferroptosis is hallmarked by disruptions in iron metabolism, redox imbalance, antioxidant system imbalance, and lipid peroxidation. Therefore, ferroptosis triggers mitochondrial impairment, inflammation, and affects several signaling pathways. As such, modulating ferroptosis holds a promising potential for preventing its deleterious effect. Resveratrol (RSV) is a promising polyphenolic compound that modulates ferroptosis due to its chelating properties. Here, we explore the preventive effects of RSV in the molecular alterations of ferroptosis. This review systematically summarizes insights about the properties of RSV in the hallmarks of ferroptosis in animal models, highlighting its beneficial effects in modulating iron metabolism, redox imbalance, glutathione metabolism, lipid peroxidation, mitochondrial impairment, signaling pathways, and inflammation. Importantly, we emphasize the promising effects of RSV in this context, indicating its relevance in further research.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515093","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":"Morin as a Modulator of Hepatic Glucose Fluxes: A Balance Between Antihyperglycemic Potential and Mitochondrial Toxicity","authors":"Letícia Fernanda Nanami,&nbsp;Eduardo Makiyama Klosowski,&nbsp;Márcio Shigueaki Mito,&nbsp;Giovana Natiele Machado Esquissato,&nbsp;Gabriel Arcanjo Viana,&nbsp;Ana Clara Oliveira Abido,&nbsp;Mariane Carneiro da Silva,&nbsp;Ana Paula da Silva Mendonça,&nbsp;Gabriele Sauthier Romano de Melo,&nbsp;Paulo Sérgio Alves Bueno,&nbsp;Francielle Pelegrin Garcia,&nbsp;Danielle Lazarin Bidoia,&nbsp;Tânia Ueda Nakamura,&nbsp;Celso Vataru Nakamura,&nbsp;Emy Luiza Ishii-Iwamoto,&nbsp;Ana Paula Ferro,&nbsp;Wanderley Dantas dos Santos,&nbsp;Osvaldo Ferrarese-Filho,&nbsp;Rogério Marchiosi,&nbsp;Rodrigo Polimeni Constantin","doi":"10.1002/jbt.70386","DOIUrl":"https://doi.org/10.1002/jbt.70386","url":null,"abstract":"<p>This study evaluated the acute effects of morin on gluconeogenesis and glycogenolysis, key metabolic pathways that maintain glycemia, in perfused rat livers. It also assessed the acute effects of morin on mitochondrial energy metabolism and toxicity in hepatic cancer cells (HepG2) and renal epithelial cells (VERO), alongside its impact on the activity of key enzymes. Liver perfusion experiments assessed glucose fluxes, oxygen consumption, adenine nucleotide levels, and enzyme activities. Isolated mitochondria evaluated the effects of morin on oxidative phosphorylation. Enzymatic assays and MTT tests conducted in vitro determined the effects on hepatic enzymes and cell viability. In perfused rat livers, morin generally inhibited gluconeogenesis from various substrates, stimulated glycogenolysis and glycolysis, and altered oxygen consumption. Experiments on morin biotransformation suggested that this process may contribute to the inhibition of gluconeogenesis. Moreover, morin inhibited citric acid cycle activity under gluconeogenic conditions and reduced cellular ATP/ADP and ATP/AMP ratios under both gluconeogenic and glycogenolytic conditions. The elevated activity of cytosolic and mitochondrial enzymes in the effluent from perfused livers indicated impaired membrane integrity. In isolated rat liver mitochondria, morin inhibited the electron transport chain, the ATP/ADP exchange system, and functioned as an uncoupling agent of oxidative phosphorylation, thereby reducing ATP synthesis. Under in vitro conditions, morin inhibited the activity of glucose 6-phosphatase, glucokinase, glucose 6-phosphate dehydrogenase, and pyruvate kinase from rat livers. At the cellular level, morin decreased the viability of HepG2 and VERO cells, indicating its toxicity. The increased glucose release due to heightened glycogenolysis, combined with the suppression of gluconeogenesis, may impact the expected antihyperglycemic effects of morin. These outcomes were partly attributed to mitochondrial bioenergetic disruption, which is an important consideration for the therapeutic use of morin, particularly with prolonged treatment or higher doses. Together, these findings highlight morin's potential as an antihyperglycemic agent but also reveal significant concerns regarding its mitochondrial toxicity.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515133","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":"Modulation of the Nrf2/HO-1 Pathway- and Apoptosis-Related Genes Following 5-hydroxymethylfurfural Induced Mouse Liver Injury","authors":"Hatice Kurtel,&nbsp;Yasemin Aydin,&nbsp;Banu Orta Yilmaz","doi":"10.1002/jbt.70385","DOIUrl":"https://doi.org/10.1002/jbt.70385","url":null,"abstract":"<p>Food contaminants released from heat-treated foods have been an issue of global investigation in recent years. The risk and toxicity assessment of 5-hydroxymethylfurfural (HMF), which is mostly exposed to through food consumption, is also of great importance. Studies have revealed the toxicity of HMF on various tissues and systems. However, there are not enough studies on the toxic effects of HMF on the liver. This study applied different doses of HMF (30 and 300 mg/kg) to adult mice for 21 days. Liver tissues obtained from mice exposed to HMF were examined histologically and histopathologically. The investigation of oxidative damage in HMF-induced liver tissue involved the spectrophotometric measurement of malondialdehyde, hydroxyl radicals, and hydrogen peroxide levels and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione, gamma glutamyl transpeptidase, and glutathione-S-transferase. The expression levels of genes associated with the Nrf2/Keap1/HO-1 signaling pathway were examined. Furthermore, oxidative stress-related genes and important genes in the apoptotic pathway were analyzed for their expression levels. The findings indicated that HMF-induced histological alterations, including abnormalities, fatty degeneration, and inflammation in hepatocytes. Furthermore, HMF caused hepatotoxicity by negatively affecting the parameters related to oxidative stress. The results revealed that HMF elevated the expression levels of apoptotic genes in liver tissue and decreased the expression levels of antiapoptotic genes, thus promoting apoptosis. These results provide new evidence that HMF exerts its toxic effect on the liver through modulation of the Nrf2 signaling pathway and subsequent induction of oxidative stress and promotion of apoptotic processes.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515092","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":"Integrated Network Toxicology and Experimental Validation Reveal the Mechanism of Bisphenol A-Induced Kidney Injury: Targeting Macrophage Esr1 Expression and Apoptosis","authors":"Ting Chen,&nbsp;Hongtao Chen,&nbsp;Ye Cheng,&nbsp;Jiahao Chen,&nbsp;Shaoling Lin,&nbsp;Lu Liu,&nbsp;Xiaoying Zhan,&nbsp;Pei Liu,&nbsp;Guiling Xie,&nbsp;Kun Xia,&nbsp;Xianli Gao,&nbsp;Yanna Chen,&nbsp;Caiyun Guo,&nbsp;Wenjun Li,&nbsp;Wenjun Ning,&nbsp;Wenli Deng,&nbsp;Jun Zhou,&nbsp;Youling Fan,&nbsp;Peng Sun","doi":"10.1002/jbt.70348","DOIUrl":"https://doi.org/10.1002/jbt.70348","url":null,"abstract":"<div>\u0000 \u0000 <p>Bisphenol A (BPA), an endocrine-disrupting chemical ubiquitously present in environmental matrices, has emerged as a critical public health concern due to its potential multiorgan toxicity. Although epidemiological and experimental evidence associates BPA exposure with diverse pathologies including metabolic syndrome, carcinogenesis, and hepatorenal dysfunction, the molecular pathogenesis underlying BPA-induced nephrotoxicity remains poorly characterized. To systematically elucidate these mechanisms, we employed an integrative network toxicology approach interrogating multiple pharmacological databases (ChEMBL, STITCH) and disease repositories (GeneCards, OMIM) to identify putative molecular targets. Through rigorous protein-protein interaction network construction (STRING database, Cytoscape), three pivotal hub genes (Esr1, Esr2, Cyp19a1) were prioritized for further investigation. Subsequent multi-omics interrogation encompassed functional enrichment analysis (GO/KEGG), molecular docking simulations, Summary data-based Mendelian randomization (SMR), and immune infiltration analysis. Notably, macrophage-specific Esr1 downregulation was identified as a key molecular event in BPA-exposed renal. Both in vivo and in vitro experiments demonstrated that BPA-mediated Esr1 suppression significantly impaired renal filtration capacity and promoted pro-inflammatory macrophage apoptosis. These findings collectively demonstrate that estrogen receptor alpha (Esr1) serves as a critical molecular nexus linking environmental BPA exposure to macrophage apoptosis-driven renal pathophysiology.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515113","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":"Zebularine Ameliorates Imiquimod-Induced Psoriasis by Inhibiting Oxidative Stress and Inflammation With Concomitant Inhibition of NF-κB/MAPK and DNMT1","authors":"Ankita Sood,&nbsp;Srinidhi Chintalapani,&nbsp;Shivam Sharma,&nbsp;Kulbhushan Tikoo","doi":"10.1002/jbt.70364","DOIUrl":"https://doi.org/10.1002/jbt.70364","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, we evaluated the impact of a potent DNA methyl transferase (DNMT) inhibitor zebularine on imiquimod-induced psoriatic mice, revealing its efficacy in mitigating hyperproliferation and keratinocyte differentiation. Molecular analyses demonstrated a marked inhibition of p38, ERK, and JNK signaling pathways, accompanied by a notable reduction in proliferative markers such as Ki-67. The crucial regulator of keratinocyte proliferation, Ki-67, exhibited significant downregulation upon zebularine treatment. Moreover, significant anti-inflammatory effects were evident through the suppression of the imiquimod-induced p65 NF-κB signaling cascade. This robust inhibition extended to the reduction in the cytokine storm associated with psoriasis-like skin inflammation. Consequently, there was a restoration of the normal epidermal architecture, accompanied by a decrease in epidermal hyperplasia and splenomegaly. Importantly, zebularine's inhibition of DNMT1 underscores its role in modulating epigenetic pathways. By altering DNA methylation, zebularine might effectively inhibit the expression of genes responsible for both inflammation and proliferation, contributing to improved skin structure. These findings collectively highlight zebularine's potential as a therapeutic agent in the management of psoriasis, supported by its anti-inflammatory effects and observed inhibition of DNMT1.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482378","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":"COTE1 Regulates AMPKα2 Deubiquitination by Targeting WWP1 Activation to Promote Proliferation and Autophagy in Small Cell Lung Cancer","authors":"Yuhui Ma,&nbsp;Bin Song,&nbsp;Hongxia Guo,&nbsp;Ying Chen,&nbsp;Caihong Cao,&nbsp;Yuchen Hao,&nbsp;Yanmin Zheng,&nbsp;Xu Li","doi":"10.1002/jbt.70342","DOIUrl":"https://doi.org/10.1002/jbt.70342","url":null,"abstract":"<p>COTE1 expression is significantly upregulated in small cell lung cancer (SCLC) tissues compared to normal lung tissues and promotes SCLC cell proliferation and migration. However, the mechanism by which COTE1 promotes these behaviors in SCLC is unclear. This study aimed to explore the role and mechanism of COTE1 in promoting the progression of SCLC and to identify potential targets for the clinical treatment of SCLC. The cells were transfected with the COTE1 overexpression plasmid or WWP1 overexpression plasmid (WT, MUT), etc., and the expression of AMPKα2 was detected via qRT-PCR and western blotting. Double immunofluorescence staining was used to observe the colocalization of COTE1 and WWP1, and protein interactions between COTE1 and WWP1 were analyzed via Co-IP. CCK-8, cell colony formation, scratch wound healing, and Transwell assays were used to assess cell proliferation, migration, and invasion. Transmission electron microscopy was used to observe cell autophagy, and western blotting was used to analyze the expression of the autophagy-related proteins AMPKα2 and p-ULK1 (Ser555). A mouse model was used to verify the effects of COTE1 on SCLC tumor growth and autophagy. We found via cell-based and In Vivo experiments that COTE1 binds to WWP1 and that high expression of COTE1 alters WWP1 expression, which in turn mediates AMPKα2 deubiquitination and promotes SCLC cell proliferation, migration, tumorigenicity, and autophagy. The overexpression of WWP1 (MUT) reversed the above effects of COTE1 on SCLC cells. In conclusion, COTE1 regulates AMPKα2 deubiquitination by targeting WWP1 activation to promote the proliferation and autophagy of SCLC cells.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70342","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482377","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":"Transcription Factor Activating Enhancer-Binding Protein 4/Acidic Nuclear Phosphoprotein 32 Family Member E Axis Increases Lactate Production to Promote Triple-Negative Breast Cancer Stemness","authors":"Xiaolin Xia,&nbsp;Sha He,&nbsp;Zhuo Chen,&nbsp;Zhou Chen,&nbsp;Jie Zhou,&nbsp;Shuyang Deng,&nbsp;Xiaolong Zao,&nbsp;Shuai Chen","doi":"10.1002/jbt.70350","DOIUrl":"https://doi.org/10.1002/jbt.70350","url":null,"abstract":"<div>\u0000 \u0000 <p>Tumor growth, metastasis, and therapy are significantly affected by cancer stem cells. Dysregulation of acidic nuclear phosphoprotein 32 family member E (ANP32E) expression is associated with the progression of various human malignancies. Furthermore, ANP32E promotes tumor stemness. Uncertainty persists regarding the role of ANP32E in triple-negative breast cancer (TNBC) as well as the molecular processes controlling cancer stemness. The expression of ANP32E in triple-negative breast cancer was detected by bioinformatics analyses and molecular experiments. The correlation analysis of ANP32E and glycolysis pathway marker genes (pyruvate dehydrogenase kinase 1 (PDK1), MYC, and hexokinase 2 (HK2)) and stemness index was conducted to identify the potential transcription factor upstream of ANP32E and binding sites. The dual luciferase assay and chromatin immunoprecipitation (ChIP) confirmed their binding relationship. Stemness was evaluated by assessing cell cloning ability, cell sphere formation ability, and expression of stem cell markers CD133, Nanog, and CD44. Cell glycolysis ability was analyzed by measuring extracellular acidification rate (ECRA), glucose consumption, lactate production, adenosine triphosphate (ATP) level, and LDHA expression. TNBC had an upregulated level of ANP32E, and ANP32E knockdown reduced TNBC cell stemness. ANP32E was positively correlated with the marker genes of glycolysis (PDK1, MYC, and HK2). Overexpression of ANP32E stimulated the glycolysis of tumor cells and raised lactate production. Furthermore, the transcription factor activating enhancer-binding protein 4 (TFAP4) was an upstream regulatory factor of ANP32E. By binding to ANP32E and activating its transcription, TFAP4 increased lactate production through the glycolysis pathway, which in turn promoted the stemness of TNBC. This study revealed a novel mechanism by which the TFAP4/ANP32E axis promotes tumor cell stemness in TNBC through the elevation of lactate production, indicating that the TFAP4/ANP32E axis may serve as a potential target for the TNBC treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473241","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":"Berberine-Induced Cytotoxicity in Breast Cancer Is Mediated by Reversal of EMT and Repression of Sirtuin 1/AKT Signaling Pathways","authors":"Nahla E. El-Ashmawy,&nbsp;Eman G. Khedr,&nbsp;Samar A. El-Adawy,&nbsp;Naglaa F. Khedr","doi":"10.1002/jbt.70375","DOIUrl":"https://doi.org/10.1002/jbt.70375","url":null,"abstract":"<div>\u0000 \u0000 <p>Epithelial-to-mesenchymal transition (EMT) is an essential process by which tumor cells undergo metastasis. Berberine (Berb), a natural isoquinoline alkaloid, has exhibited antitumor properties against a wide range of cancer types. This study was conducted to investigate the underlying molecular mechanisms of the antitumor effect of berberine in the presence and absence of sirtuin-1 inhibitor (sirtinol; Sirt) in vivo in mice bearing solid Ehrlich carcinoma (SEC) and in vitro in triple-negative breast cancer (TNBC) cells. The mice were classified into four groups 12 days after the inoculation of SEC cells into the mice to induce breast cancer. These groups were as follows: the untreated SEC group (mice were administered the vehicle), the Sirt group (1 mg/kg), the Berb group (10 mg/kg), and the cotreatment Sirt/Berb group. For 16 days, they were administered on a daily basis. TNBC MDA-MB-231 cells were displayed in a 48-h treatment containing 25 μM Sirt, 23 μM Berb, or a combination of the two. Berb and/or Sirt attenuated EMT as proven via the upregulation of E-cadherin expression and downregulation of vimentin and sirtuin-1 expression in both in vitro and in vivo experiments. These outcomes were correlated with reduced p-AKT/AKT and vascular endothelial growth factor receptor₂ (VEGFR₂), along with retardation of cancer progression. The antitumor activity of Berb towards breast cancer was evidenced in vivo and in vitro and could be, in part, through EMT's inhibition and suppression of sirtuin-1 and AKT cascades.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472976","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":"SP1-Mediated Upregulation of KIF4A Promotes Prostate Cancer Progression via Targeting TWIST1","authors":"Xiaofei Liu,&nbsp;Shaoke Li,&nbsp;Zhi Wang,&nbsp;Qi Zhao","doi":"10.1002/jbt.70378","DOIUrl":"https://doi.org/10.1002/jbt.70378","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Previous studies have found the highly expressed kinesin family member 4A (KIF4A) in various tumors, including prostate cancer. However, the role of KIF4A and its potential mechanisms in the development of prostate cancer remains unclear. Bioinformatics analysis was used to analyze the levels of KIF4A and TWIST-related protein 1 (TWIST1) based on the data from TCGA, HPA, and ENCORI databases. RT-qPCR was performed to measure the mRNA expression of KIF4A and TWIST1. The protein expression of KIF4A and specificity protein 1 (SP1) was examined through western blot analysis. CCK-8, EdU, and colony formation assay were carried out to evaluate the proliferative ability. The invasive and migrated cells were determined using the Transwell invasion assay and the wound-healing assay, respectively. EMT progress was evaluated by detecting E-cadherin and N-cadherin expression using western blot analysis. The relationship between SP1 and KIF4A was verified using ChIP and dual-luciferase reporter assay. The interaction between KIF4A and TWIST1 was confirmed through Co-IP. Animal experiments and IHC were carried out to explore the effects of KIF4A on prostate cancer mice in vivo. KIF4A was increased in prostate cancer tissues and cells, and KIF4A knockdown suppressed the proliferative, invaded, and migrated abilities, as well as EMT in DU145 and PC3 cells. The inhibition effects of SP1 knockdown on cell proliferation, invasion, migration, and EMT were harbored by overexpressing KIF4A. TWIST1 was elevated in prostate cancer and positively regulated by KIF4A. TWIST1 upregulation reversed the repressive impacts of KIF4A downregulation on prostate cancer progression. In addition, in vivo experiments and IHC assay indicated that KIF4A depletion inhibited tumor growth and EMT in mice. Our findings suggested that SP1 activated KIF4A to regulate TWIST1 expression, thereby promoting the development of prostate cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473240","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":"Inhibition of circ_0127646 Enhanced the Cisplatin Sensitivity in Osteosarcoma Cells via miR-22/KAT6B Axis","authors":"Menghan Chang,&nbsp;Qian Chen,&nbsp;Chang Sun,&nbsp;Xin Shi,&nbsp;Sujia Wu,&nbsp;Linfeng Zheng,&nbsp;Xing Zhou","doi":"10.1002/jbt.70381","DOIUrl":"https://doi.org/10.1002/jbt.70381","url":null,"abstract":"<div>\u0000 \u0000 <p>Effective chemotherapy could improve the survival rate of patients with osteosarcoma (OS), but the efficacy of such treatments is often compromised by the development of drug resistance. Circular RNAs are known to exert pivotal regulatory functions in the chemoresistance of multiple tumor cells. The present study was designed to investigate the role and underlying mechanism of circ_0127646 in modulating the chemosensitivity of OS cells to cisplatin. We observed a marked upregulation of circ_0127646 in OS cell lines (HOS, MG63, U2OS, and OS9901) following cisplatin treatment. Silencing of circ_0127646 by a small interfering RNA (si-circ) enhanced cisplatin-induced apoptosis and diminished clonogenic capacity in MG63 and OS9901 cells. Moreover, the sensitizing effect of si-circ to cisplatin in OS cells was counteracted by si-miR-22. Inhibition of circ_0127646 augmented the suppressive effect of miR-22 on KAT6B expression, leading to a reduction in the expression levels of some cytokines, including S100A8, S100A9, PDGF, and VEGF. This reduction, in turn, inhibited the activation of PI3K/Akt/mTOR signaling pathway, thereby sensitizing OS cells to cisplatin. Collectively, our findings indicated that inhibition of circ_0127646 could enhance the chemosensitivity of OS cells to cisplatin via miR-22/KAT6B axis. Circ_0127646 might serve as a prognostic biomarker for cisplatin-based therapies and a potential therapeutic target in OS.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473239","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}