Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Induction of miR-224 by Reactive Oxygen Species Regulates RASSF6 and Thus Modulates Malignant Behaviors and Chemosensitivity in Esophageal Squamous Cell Carcinoma","authors":"Yi Liu,&nbsp;Yina Wang,&nbsp;Adili Salai,&nbsp;Yueying Yang,&nbsp;Yang Wang","doi":"10.1002/jbt.70105","DOIUrl":"https://doi.org/10.1002/jbt.70105","url":null,"abstract":"<p>Esophageal cancer is one of the most common malignant tumors of the digestive tract, and miR-224 can promote the hypoxia tolerance of esophageal cancer cells. The expression of miR-224 and HIF-1α in esophageal cancer cells under hypoxic induction and their relationship with ROS was studied using RT-qPCR and Western Blot assays; cell viability and apoptosis under hypoxia, as well as the effects of miR-224 on cell proliferation and drug resistance, were investigated using CCK8, Annexin V-FITC/PI, H2DCFDA staining and Western Blot assays. Under hypoxic induction, miR-224 and HIF-1α expressions were upregulated, with the upregulation of miR-224 being related to ROS accumulation, while HIF-1α upregulation was not affected by ROS. Furthermore, the upregulation of miR-224 facilitated the survival of esophageal cancer cells under hypoxic conditions and reduced their chemosensitivity to CDDP. This effect was also validated in vitro, as miR-224 overexpression promoted the malignant behaviors in ESCC cells. Under hypoxic induction, ROS accumulation can lead to the upregulation of miR-224. MiR-224 facilitates the survival of esophageal cancer cells under hypoxic conditions and induces chemotherapeutic drug resistance.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595143","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":"HC070, a Transient Receptor Potential Canonical 5 (TRPC5) Channels Inhibitor Ameliorated α-synuclein Preformed Fibrils-Induced Parkinson's Disease: A Neurobehavioural and Mechanistic Study","authors":"Bhupesh Vaidya,&nbsp;Soumojit Biswas,&nbsp;Ipsita Roy,&nbsp;Shyam Sunder Sharma","doi":"10.1002/jbt.70207","DOIUrl":"https://doi.org/10.1002/jbt.70207","url":null,"abstract":"<div>\u0000 \u0000 <p>Alpha-synuclein pathology is a characteristic feature of Parkinson's disease (PD) and related synucleinopathies. As a result, reducing alpha-synuclein pathology is one of the mechanisms being looked at for the development of newer agents which target these diseases. In the present study, we investigated the potential of HC070, a transient receptor potential canonical 5 (TRPC5) channel inhibitor in reducing alpha-synuclein pathology in PD. TRPC5 channels are activated in response to oxidative stress and mediators of apoptosis (calpain), the processes are also closely linked to alpha-synuclein toxicity. Using exposure of alpha synuclein-preformed fibrils to the Sprague Dawley rats and SH-SY5Y cells, we induced PD in in vitro and in vivo model systems. It was followed by the estimation of behavioural deficits, molecular parameters and biochemical estimations. Results of our experiments revealed that animals treated intraperitoneally with HC070 exhibited reduced alpha-synuclein levels accompanied by improvement in tyrosine hydroxylase levels, mitochondrial health and reduction in oxidative stress and calpain signalling. Furthermore, HC070 administration also caused a reduction in the TRPC5 levels along with improvement seen in motor and cognitive deficits. Similar protection was observed with HC070 in SH-SY5Y cells exposed to alpha-synuclein PFF. Overall, our study demonstrates the novel role of inhibition of TRPC5 channels in the reversal of alpha-synuclein toxicity and associated PD pathology.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595041","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":"Correction to “Synthesis and Investigation of Antibacterial Properties of Thymol, Carvacrol, Eugenol, and Perillyl Alcohol Based ß-Halo Alcohol and ß-Halo Thiol Compounds”","authors":"","doi":"10.1002/jbt.70228","DOIUrl":"https://doi.org/10.1002/jbt.70228","url":null,"abstract":"<p>Çakmak, F., Toptan, H., Genc Bilgicli, H., Köroğlu, M., &amp; Zengin, M. (2025). Synthesis and Investigation of Antibacterial Properties of Thymol, Carvacrol, Eugenol, and Perillyl Alcohol Based β-Halo Alcohol and β-Halo Thiol Compounds. Journal of Biochemical and Molecular Toxicology, 39(2), e70171. https://doi.org/10.1002/jbt.70171</p><p>The acknowledgement part as written “This research was partly supported by the Research Fund of Sakarya University (Project Number: 2023-19-44-45).” should be changed as “This research was supported by YÖK 100/2000 Doctoral Scholarship Program and partly supported by Research Fund of Sakarya University (Project Number: 2023-19-44-45).”</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595142","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":"Characterization of LINC00483 as a Novel Oncogene in Colorectal Cancer via Targeting miR-601/TSPAN8 Signaling Axis","authors":"Xiao Liu,&nbsp;Hui Xiong,&nbsp;Tie Chen,&nbsp;Xue Qiu","doi":"10.1002/jbt.70164","DOIUrl":"https://doi.org/10.1002/jbt.70164","url":null,"abstract":"<div>\u0000 \u0000 <p>LINC00483 is exerted a crucial function in many malignant tumors' progression, but the role of LINC00483 in colorectal cancer (CRC) carcinogenesis remains not fully understood. The aim of our study was to explore the potential role of LINC00483 in the development of CRC and its underlying molecular mechanism. In the present study, the level of mRNA and protein was assessed through using qRT-PCR and Western blot analysis assays. Cell proliferation was assessed by using Cell Counting Kit-8 (CCK-8) and colony formation assays. The cell metastasis was assessed by using transwell assays. Results revealed that LINC00483 was elevated in CRC tissue and cell lines. Upregulation of LINC00483 was negatively correlated with the overall survival. The mRNA expression of tetraspanin 8 (TSPAN8) is increased in CRC tissues, whereas the expression of miR-601 is decreased, and in CRC tissues, a correlation between the expression levels of LINC00483 and TSPAN8 was positive, but the correlation between LINC00483 and miR-601 was negative. LINC00483 deficiency could inhibit the cell proliferation, migration, and invasion in CRC cell lines. Moreover, the proliferation, migration, and invasion were inhibited in CRC cell lines after transfected with miR-601 mimics; but this effect could be eliminated by LINC00483 overexpressed. Results also suggested that the protein expression of TSPAN8 and N-cadherin is decreased in CRC cell lines after transfected with miR-601 mimics, whereas the protein expression of E-cadherin is increased; but this effect could be abrogated by LINC00483 overexpressed, which means that miR-601 mimics can inhibit the metastasis of CRC, but after cotransfection with LINC00483, the metastasis ability of CRC is restored. In conclusion, our study elucidated that LINC00483 promote the CRC progression by upregulating TSPAN8 via sponging miR-601. This finding provided a new potential drug target for the treatment of CRC in clinic.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581380","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 Trends in Modulation of Transient Receptor Potential Canonical 6 Channels as Therapeutic Targets","authors":"Ayush Sharma,&nbsp;Snehal Patel,&nbsp;Mithun Singh Rajput","doi":"10.1002/jbt.70203","DOIUrl":"https://doi.org/10.1002/jbt.70203","url":null,"abstract":"<div>\u0000 \u0000 <p>The transient receptor potential canonical (TRPC) channel family includes TRPC6, a nonselective receptor-activated cation channel. Its activation result in Ca²⁺, Na⁺ along with other cationic ion influx and the phosphorylation of tyrosine, serine and phosphoinositides regulates TRPC6. The channel is widely distributed and plays physiological role in different body parts such as kidney, lungs, blood vessels, heart, brain, intrinsic cardiac ganglia and eye. It has been determined that TRPC6 is a crucial part of the kidney podocytes. Mutation in TRPC6 gene results in focal segmental glomerulosclerosis. A significant function of TRPC6 is also witnessed in the pathogenesis of various cancers including breast, esophageal, renal, head and neck squamous cell carcinoma. TRPC6 channel is found to be overexpressed in the macrophages of chronic obstructive pulmonary disorder and has a role in cardiac hypertrophy. In last decade many natural, semi synthetic and synthetic pharmaceutical agents modulating TRPC6 activity have been investigated which can be alucrative approach for the prevention and treatment of diseases associated with TRPC6 channel downregulation and upregulation. Therefore, present review aims to summarize the involvement of TRPC6 with its Ca²⁺ dependent effect in different physiological and pathological conditions with the downregulation as well as upregulation of TRPC6 channel functions and summarizes the progress achieved in those investigations pertaining to modulators of TRP6 channels.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581377","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":"Repurposing Secukinumab and Dapagliflozin as Candidate Therapies to Mitigate the Renal Toxicity of Sunitinib in Rats Through Suppressing IL-17-Mediated Pyroptosis and Promoting Autophagy","authors":"Rania A. Elrashidy,&nbsp;Hoda E. Mohamad,&nbsp;Sara M. Abdel Aal,&nbsp;Samar R. Mohamed,&nbsp;Sara M. Tolba,&nbsp;Yasmin K. Mahmoud","doi":"10.1002/jbt.70204","DOIUrl":"https://doi.org/10.1002/jbt.70204","url":null,"abstract":"<div>\u0000 \u0000 <p>Sunitinib (SUN) is a chemotherapeutic agent showing renal toxicity that limits its clinical applications. The present research aimed to clarify the potential ameliorative effects of secukinumab (SEC) and dapagliflozin (DAPA) against SUN-induced renal toxicity and the underpinning molecular mechanisms. For this purpose, adult Wistar albino rats were received SUN (25 mg/kg 3 times/week, <i>po</i>) and co-treated with SEC (3 mg/kg/every 2 weeks, subcutaneously) or DAPA (10 mg/kg/day, <i>po</i>) for 4 weeks and compared with age-matched control group (CON). Markers of kidney functions were assessed in serum samples. Kidneys were harvested for biochemical and histological examination. Compared to CON group, SUN-treated rats displayed signs of kidney dysfunction along with renal histological changes that were ameliorated by SEC or DAPA. Both drugs significantly lowered the renal levels of IL-17, but SEC exerted more inhibitory effect than DAPA. Additionally, SUN-subjected rats showed significant increases in the renal expression of NLRP3 inflammasome and the other inflammatory mediators including IL-1β, END-1, and MCP-1. This was associated with marked decline of the renal levels of beclin-1. Co-treatment with SEC or DAPA significantly suppressed NLRP3-induced inflammation while enhanced beclin-1-mediated autophagy. The modulatory effect of DAPA on NLRP3 and beclin-1 was superior to that of SEC. Moreover, both drugs significantly and similarly attenuated the enhanced cleaved caspase-3 expression and interstitial fibrosis in renal tissue of SUN-subjected rats. Collectively, these findings may repurpose SEC and DAPA as candidate therapies to alleviate the renal toxicity of SUN and to rescue the renal functionality in SUN-treated cancer cases.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581379","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":"Dimethyl Fumarate Attenuates Cyclophosphamide-Induced Bladder Damage and Enhances Cytotoxic Activity Against SH-SY5Y Cells","authors":"Elif Nur Barut,&nbsp;Seçkin Engin,&nbsp;Elif Öz,&nbsp;Rengin Reis","doi":"10.1002/jbt.70212","DOIUrl":"https://doi.org/10.1002/jbt.70212","url":null,"abstract":"<p>Cylophosphamide (CP)-induced acute cystitis is a debilitating bladder dysfunction commonly observed in cancer patients, primarily resulting from oxidative damage and inflammation in the bladder tissue. Dimethyl fumarate (DMF) is a fumaric acid ester approved for the treatment of multiple sclerosis due to its antioxidant and anti-inflammatory properties. Thus, we aimed to investigate the multiple effects of DMF, involving both its potential synergistic effect with CP on the SH-SY5Y cells and its uroprotective effect on CP-induced acute cystitis. Female Balb/c mice were orally administrated DMF (100 or 300 mg/kg/day) for five consecutive days before a single intraperitoneal (i.p) dose of CP. Mesna was administered 20 min before and at 4 h, 8 h after CP application. Following 24 h of CP injection, bladders were removed for functional, biochemical analysis and evaluation of vesical vascular permeability. SH-SY5Y cell viability was assayed by MTT test. CP markedly decreased carbachol-induced contraction of detrusor strips (<i>p</i> &lt; 0.01), which was prevented by the high-dose DMF treatment (<i>p</i> &lt; 0.05). Evans blue dye extravasation was greatly increased in the bladders of cystitis group (<i>p</i> &lt; 0.001), which was significantly decreased in DMF-treated mice with cystitis (<i>p</i> &lt; 0.01). Total GSH content was decreased (<i>p</i> &lt; 0.01) whereas TNF-α level was increased (<i>p</i> &lt; 0.05) in the bladders of cystitis group. High-dose DMF-treated mice showed an increment in total GSH content (<i>p</i> &lt; 0.05) without any alterations on TNF-α levels of the bladders with cystitis. Additionally, combination of different concentrations of CP and DMF exhibited a potent synergistic cytotoxic effect in SH-SY5Y cells. DMF improved CP-induced acute cystitis by partially suppressing oxidative stress and inflammation, while also enhancing the cytotoxic effects of CP.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581378","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":"Molecular Mechanisms of Neutrophil Extracellular Traps in Promoting Gastric Cancer Epithelial–Mesenchymal Transition Through SERPINE-1 Expression","authors":"Zhen Ma,&nbsp;Xiaolin Li,&nbsp;Shifeng Yang,&nbsp;Hao Yang,&nbsp;Ange Zhang,&nbsp;Nana Li,&nbsp;Xiaoming Zou","doi":"10.1002/jbt.70157","DOIUrl":"https://doi.org/10.1002/jbt.70157","url":null,"abstract":"<p>Gastric cancer remains a significant global health concern, with its progression and metastasis often associated with epithelial–mesenchymal transition (EMT). This study investigated the role of neutrophil extracellular traps (NETs) in promoting gastric cancer EMT by regulating SERPINE-1 expression, which encodes plasminogen activator inhibitor-1 (PAI-1). Western blot and immunohistochemistry were used to detect protein expression. Cell Counting Kit-8 was tested for cell proliferation ability using clones. The SERPINE-1 gene was knocked down using lentivirus. Immunofluorescence was used to detect the co-expression of proteins, and a Transwell assay and wound-healing assay were used to investigate the migration ability of cells. Experimental conclusions were verified in vivo using a nude mouse model. We first demonstrated overexpression of PAI-1 in gastric cancer tissues and cell lines. Subsequently, we found that NETs significantly enhanced the expression of EMT-related markers. These changes were accompanied by increases in cell invasion, migration, proliferation and tumour sphere formation. To further elucidate the mechanism, we employed lentivirus-mediated SERPINE-1 knockdown to reverse NET-induced EMT phenotype effectively. Mechanistically, we found that NETs activated the transforming growth factor (TGF)-β signalling pathway via PAI-1 as evidenced by increased expression of TGF-β1, TGF-βR1, TGF-βR2, phosphorylated Smad2/3 and Smad4. Finally, in vivo experiments using a nude mouse model of gastric cancer liver metastasis confirmed that NET-treated HGC-27 cells exhibited enhanced metastatic potential and SERPINE-1 knockdown abrogated metastatic potential. Our findings reveal a novel mechanism by which NETs promote EMT and metastasis in gastric cancer via the PAI-1–TGF-β axis. PAI-1 can be used as a potential target for the treatment of gastric cancer, and the expression of PAI-1 is closely related to the prognosis of patients with gastric cancer. Therapeutic strategies targeting NETs or PAI-1 may help prevent EMT and metastasis of gastric cancer and improve clinical outcomes in patients.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581928","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":"Vitamin D and Dapagliflozin Alleviate Renal Injury and Insulin Resistance in a Diet-Induced Metabolic Syndrome Rat Model","authors":"Xincai Hong,&nbsp;Yongbin Ma,&nbsp;Weihong Yang,&nbsp;Yikun Li,&nbsp;Xiufang Tang,&nbsp;Zhaoxia Wang","doi":"10.1002/jbt.70185","DOIUrl":"https://doi.org/10.1002/jbt.70185","url":null,"abstract":"<div>\u0000 \u0000 <p>Metabolic syndrome, primarily driven by high-fat/high-sugar (HF/HS) diets, is closely linked to insulin resistance and renal injury, leading to serious complications such as type 2 diabetes mellitus and diabetic nephropathy. This study explored the combined effects of Vitamin D (VD) and dapagliflozin (Dap) on metabolic and renal complications in an HF/HS diet-induced rat model of metabolic syndrome. The combination therapy significantly improved insulin sensitivity, reduced fasting blood glucose levels, and alleviated renal injury markers such as blood urea nitrogen and creatinine. It also attenuated inflammation, lipid accumulation, and endoplasmic reticulum stress in renal tissues, as evidenced by reduced levels of inflammatory cytokines and key stress markers (GRP78 and CHOP). Importantly, the study highlights the novel synergistic potential of VD and Dap in addressing these complications through complementary mechanisms. These findings suggest that this combination therapy offers promising clinical potential for managing metabolic syndrome and its progression to severe complications.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565020","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":"SALL4/ABCB6 Axis Suppresses Ferroptosis in Colon Cancer by Mediating Mitophagy","authors":"Leilei Yang,&nbsp;Yuehuai Xu,&nbsp;Jiaju Han,&nbsp;Chengfeng Fang,&nbsp;Zaiping Yang,&nbsp;Ruili Zhang,&nbsp;Shenkang Zhou","doi":"10.1002/jbt.70183","DOIUrl":"https://doi.org/10.1002/jbt.70183","url":null,"abstract":"<div>\u0000 \u0000 <p>According to reports, the inhibition of ferroptosis is an essential culprit of malignant progression in various tumors, including colon cancer (CC). However, the relevant study on the regulatory mechanism of CC ferroptosis is sparse. This project was designed to identify the key genes modulating CC ferroptosis as well as specific mechanisms. Based on The Cancer Genome Atlas (TCGA)-CC mRNA expression data and immunohistochemistry assay, we analyzed the expression of ABCB6 and SALL4 in CC tissue. The HTFtarget was employed to predict the binding sites. The expression of ABCB6 and SALL4 in CC cells was analyzed by quantitative polymerase chain reaction, and the interaction between ABCB6 and SALL4 was verified by dual-luciferase and chromatin immunoprecipitation experiments. Cell viability was tested by cell counting kit-8 and colony formation assay. The malondialdehyde (MDA), Fe²⁺ content, and lipid reactive oxygen species (ROS) levels were examined by utilizing the corresponding reagent kits. The protein expression of ABCB6, SALL4, GPX4, GCLC, and SLC3A2 were determined via western blot. High expression of ABCB6 was detected in CC. ABCB6 overexpression suppressed ferroptosis and dramatically declined the levels of MDA, lipid ROS, and Fe²⁺ in cells. Furthermore, it induced mitochondrial membrane potential dysfunction and substantially suppressed the fluorescence intensity of GFP-LC3, which in turn promoted the expression of GPX4, GCLC, and SLC3A2 proteins and prevented CC cell ferroptosis. The cell rescue experiment verified that SALL4 initiated ABCB6 activation to mediate mitophagy and prevent ferroptosis in CC cells. The findings evidenced that the SALL4/ABCB6 axis suppresses mitophagy to hinder ferroptosis in CC. The mitophagy pathway may be essential for ABCB6 to regulate ferroptosis in CC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143564966","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}