Tissue & cell最新文献

{"title":"5-Aza-CdR increases expression of the tight junction protein ZO-1 via upregulation of miR-126 through promoter hypomethylation in HMEC-1 cells","authors":"Xi Zhang ,&nbsp;Shaohan Zhang ,&nbsp;Yuzhi Shao ,&nbsp;You Liu ,&nbsp;Kerui Gong ,&nbsp;Chunyang Zhang ,&nbsp;Zhijun Zhao ,&nbsp;Xuguo Ma ,&nbsp;Gang Fu ,&nbsp;Guo Shao","doi":"10.1016/j.tice.2025.103280","DOIUrl":"10.1016/j.tice.2025.103280","url":null,"abstract":"<div><div>Cellular junctions are vital for endothelial cell (EC) function, with ZO-1 being a key tight junction protein influenced by miR-126. This study examines how 5-Aza-2′-deoxycytidine (5-Aza-CdR), a DNMT inhibitor, affects ZO-1 and miR-126 levels in HMEC-1 cells in vitro. HMEC-1 cells were treated with 5-Aza-CdR. ZO-1 expression was measured by real-time PCR and western blot. The expression level of miR-126 and its promoter DNA methylation level were determined by real-time PCR and MS-PCR. The mRNA and protein expression levels of DNMTs were detected by real-time PCR and western blot. The global methylation level was detected by 5-mC-positive signal using laser confocal microscopy and by combined bisulfite restriction analysis (COBRA) for Alu and Long interspersed element-1 (LINE-1) methylation patterns. Cell apoptotic and cell cycle were analyzed using cytometry. The expression of ZO-1 was enhanced with the upregulation of miR-126 via its promoter DNA hypomethylation. The DNMT1 and DNMT3A as well as global methylation levels were decreased with the S-phase cell cycle arrested in HMEC-1 cells which were treated with 5-Aza-CdR. This study indicated that 5-Aza-CdR can induce the ZO-1 expression related to the up-regulation of miR-126 through the DNA methylation mechanism in ECs.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103280"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in effects of anterior cruciate ligament reconstruction on marrow adipose tissue and trabecular bone in the rat proximal tibial epiphysis","authors":"Akinori Kaneguchi ,&nbsp;Marina Kanehara ,&nbsp;Kaoru Yamaoka ,&nbsp;Junya Ozawa","doi":"10.1016/j.tice.2025.103232","DOIUrl":"10.1016/j.tice.2025.103232","url":null,"abstract":"<div><div>Marrow adipose tissue (MAT) is a unique tissue that can suppress bone formation. After anterior cruciate ligament (ACL) reconstruction, bone loss and MAT accumulation are observed. Although sex differences are considered to affect bone and MAT metabolism, their effects on bone loss and MAT accumulation after ACL reconstruction are uncertain. In this study, we aimed to determine the effects of sex differences on trabecular bone loss and MAT accumulation after ACL reconstruction using an animal model. Rats were divided into male control, male ACL reconstruction, female control, and female ACL reconstruction groups. ACL reconstruction surgery was performed for the right knees of rats in the ACL reconstruction groups, while rats in the control groups did not receive knee surgery. At 1, 4, or 12 weeks after starting the experiment, changes in trabecular bone and MAT in the proximal tibial epiphysis were histologically assessed. In the male ACL reconstruction group, a relative decrease in trabecular bone area compared to sex-matched controls was observed transiently at 4 weeks, while trabecular bone area in the female ACL reconstruction group was maintained at control level throughout the experiment. MAT accumulation after ACL reconstruction occurred in both males and females; however, this change occurred at 4 weeks in males, while in females it occurred later, at 12 weeks. In conclusion, MAT accumulation after ACL reconstruction occurred earlier in males compared to females. This early MAT accumulation after ACL reconstruction in males might contribute to the transient relative decrease in trabecular bone area.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103232"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear receptor ERRγ acts as a key transcriptional regulator of hepatic LCN2 expression in CCl4-induced acute liver injury","authors":"Byungyoon Choi ,&nbsp;Yoon Seok Jung ,&nbsp;Woo-Ram Park ,&nbsp;Yong-Hoon Kim ,&nbsp;Chul-Ho Lee ,&nbsp;Hueng-Sik Choi ,&nbsp;Don-Kyu Kim","doi":"10.1016/j.tice.2025.103250","DOIUrl":"10.1016/j.tice.2025.103250","url":null,"abstract":"<div><div>Estrogen-related receptor γ (ERRγ) is a nuclear receptor and transcription factor that plays an important role in liver metabolism by regulating the transcription of genes involved in inflammation, alcohol metabolism, and iron metabolism. Lipocalin 2 (LCN2) is a secreted protein that regulates inflammation, immune response, and iron homeostasis and is involved in liver injury. However, the transcriptional regulation of LCN2 in the liver remains largely unknown. Here, we showed that ERRγ is a critical transcriptional regulator of the hepatic <em>LCN2</em> gene in carbon tetrachloride (CCl₄)-induced acute liver injury. CCl₄ treatment significantly increased hepatic <em>ERRγ</em> and <em>LCN2</em> gene expression by inducing interleukin-6 (IL-6) expression in mice. Interestingly, ERRγ overexpression increased <em>LCN2</em> gene expression and secretion in the livers of mice. Conversely, mice with the liver-specific knockout of ERRγ (ERRγ-LKO) exhibited significantly decreased CCl₄-induced <em>LCN2</em> gene expression in the liver. Moreover, IL-6 treatment increased <em>LCN2</em> expression and secretion in the livers of wild-type mice, which was significantly attenuated in ERRγ-LKO mice. Furthermore, deletion and mutation analyses revealed that ERRγ directly binds to ERR-response elements in the <em>LCN2</em> promoter, modulating <em>LCN2</em> gene transcription; these data were confirmed by a chromatin immunoprecipitation assay. Finally, administering GSK5182, an inverse agonist of ERRγ, significantly reduced the CCl₄-induced levels of LCN2 mRNA and protein in the liver. These findings suggest that ERRγ is a previously unrecognized transcriptional regulator of <em>LCN2</em> in CCl₄-mediated acute liver injury.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103250"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RBM15-mediated m6A modification upregulates KDM2A to promote ferroptosis in osteoarthritis cells","authors":"Changdong Fan ,&nbsp;Jing Ma ,&nbsp;Fengliang Fan ,&nbsp;Rongbing Yi ,&nbsp;Wenbo Wang","doi":"10.1016/j.tice.2025.103248","DOIUrl":"10.1016/j.tice.2025.103248","url":null,"abstract":"<div><h3>Background and aims</h3><div>Ferroptosis has been acknowledged to be involved in the progression of osteoarthritis (OA), contributing to chondrocyte damage and articular cartilage degradation. This investigation seeks to explain the mechanism of RBM15 in ferroptosis of OA cell models.</div></div><div><h3>Methods</h3><div>OA cell model was established using IL-1β-induced chondrocytes. After silencing RBM15 expression, TNF-α and IL-6 were detected, cell viability was measured, LDH, Fe²⁺, ROS, MDA, and GSH were assessed, and ACSL4 and SLC7A11 expression was quantified. RT-qPCR and Western blot were employed to detect the expression of RBM15, KDM2A, and HOXA2. The m6A content in cells was assayed using a kit. RIP assay was utilized to analyze m6A modification on KDM2A. Dual-luciferase assay was employed to validate RBM15-mediated m6A modification on KDM2A. RT-qPCR was applied to examine KDM2A mRNA stability. ChIP was employed to assess the enrichment of KDM2A and H3K36me2 at the HOXA2 promoter. Combined experiments were designed to elucidate the role of KDM2A and HOXA2 in ferroptosis of OA cell models.</div></div><div><h3>Results</h3><div>RBM15 and KDM2A were upregulated, while HOXA2 was reduced in IL-1β-stimulated chondrocytes. RBM15 downregulation enhanced chondrocyte viability and mitigated ferroptosis. RBM15-mediated m6A modification upregulated KDM2A, suppressed H3K36me2 enrichment at the HOXA2 promoter, and inhibited HOXA2 expression. Overexpression of KDM2A and downregulation of HOXA2 could partially counteract the suppressive effect of RBM15 silencing on chondrocyte ferroptosis.</div></div><div><h3>Conclusion</h3><div>RBM15-mediated m6A modification upregulates KDM2A to inhibit HOXA2 expression by reducing H3K36me2 enrichment, thus promoting IL-1β-induced chondrocyte ferroptosis.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103248"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigation conferred by banana flower extract against aflatoxin-induced oxidative stress, inflammation, apoptosis, molecular docking, and histological disturbances in rabbits","authors":"Fatima S. Alaryani","doi":"10.1016/j.tice.2026.103320","DOIUrl":"10.1016/j.tice.2026.103320","url":null,"abstract":"<div><div>This study investigated the protective effects of banana flower extract (BFE) against aflatoxin B1 (AFB1)-induced oxidative stress, inflammation, and immune dysfunction in growing rabbits. One hundred and twenty rabbits were divided into four experimental groups: a control group (receiving a vehicle only), an AFB1 group (receiving 0.3 mg AFB1/kg diet), a BFE group (receiving 500 mg/kg banana flower extract), and an AFB1 and BFE group for eight weeks. The results showed that exposure to AFB1 resulted in reduced growth performance, along with elevated liver enzymes, blood lipids, and renal dysfunction (P &lt; 0.05). Additionally, 8-OHdG levels were significantly higher in the AFB1 group, but BFE treatment significantly reduced this elevation (P &lt; 0.05). AFB1 also caused a significant increase in oxidative stress (as indicated by higher MDA and PC levels) and a decrease in antioxidant enzyme activity (SOD, GPx, and TAC) and immune response (IgG and IgM). Pro-inflammatory responses were significantly increased by AFB1 exposure, while BFE treatment effectively prevented apoptosis (P &lt; 0.05) and inflammation (P &lt; 0.01) in the rabbits, and significantly improving immunoglobulin synthesis (P &lt; 0.05). BFE protected against renal and intestinal structural damage induced by AFB1. Molecular docking studies revealed that gallic and protocatechuic acids interacted with BAX (binding energies: −4.17 and −6.78 kcal/mol, respectively), Caspase-3 (-4.28 and −7.38 kcal/mol, respectively), and SOD (-4.16 and −6.38 kcal/mol, respectively). These findings suggest that the compounds may play a role in modulating apoptosis and antioxidant defense. This study underscores the potential of utilizing by-product extracts, such as banana flower extract, to mitigate the adverse effects of aflatoxins in animals through their apoptotic and antioxidant properties.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103320"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boosting muscle health in aging rats: The synergistic effect of vitamin C, silymarin, and endurance swimming on a high-fat diet","authors":"Fariba Aghaei ,&nbsp;Ehsan Arabzadeh ,&nbsp;Foad Feizolahi ,&nbsp;Ali Nejati Bezdi ,&nbsp;Majid Abasi ,&nbsp;Mehdi Zargani","doi":"10.1016/j.tice.2025.103290","DOIUrl":"10.1016/j.tice.2025.103290","url":null,"abstract":"<div><h3>Background</h3><div>This paper inspects the influence of 8-week endurance swimming supplemented with vitamin C and Silymarin on histopathological changes and some gene markers of skeletal muscle hypertrophy in aged rats receiving a high-fat diet (HFD).</div></div><div><h3>Methods</h3><div>Twenty-five aged male Wistar rats underwent random allocation to five groups, including a normal diet (Control), HFD, HFD + combined vitamin C and Silymarin supplementation (HFD+CS), HFD + endurance swimming (HFD+ES), and HFD + CS + ES. After six weeks of HFD, CS was gavaged to rats as the selected intervention together with HFD in the supplementation groups over eight weeks. Besides, the exercise groups received swimming exercise training five days/week over eight weeks.</div></div><div><h3>Results</h3><div>HFD increased the lipid profile and fat penetration into the liver tissue of elderly rats. Meanwhile, endurance swimming exercises and a combined supplement significantly improved the liver tissue and regulated the lipid profile. The examination of muscle tissue and gene changes revealed that HFD could increase muscle atrophy and reduce the 4E-BP1, S6K1, and mTOR gene levels, while the combination of exercise and supplementation could increase the 4E-BP1, S6K1, and IGF-1 gene levels and improve muscle fiber diameter in aged rats.</div></div><div><h3>Conclusion</h3><div>Endurance swimming training with vitamin C and silymarin supplementation in aging NAFLD model rats can improve lipid profile factors and skeletal muscle tissue fiber diameter.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103290"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin attenuates chronic obstructive pulmonary disease by suppressing NLRP3-mediated pyroptosis in alveolar macrophages","authors":"Xiaofeng Li ,&nbsp;Zhe Wang ,&nbsp;Meng Shi ,&nbsp;Tingting Zhang ,&nbsp;Sha Huang ,&nbsp;Xiaoju Liu","doi":"10.1016/j.tice.2025.103305","DOIUrl":"10.1016/j.tice.2025.103305","url":null,"abstract":"<div><div>Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation and emphysema and is induced primarily by cigarette smoke (CS) exposure. Emerging evidence suggests that alveolar macrophage (AM) pyroptosis contributes to COPD pathogenesis; however, the underlying mechanisms are incompletely understood. Moreover, although melatonin is known to have therapeutic potential for COPD, whether the regulation of AM pyroptosis contributes to its therapeutic effects remains unclear. Here, we investigated the mechanism by which AM pyroptosis participates in COPD airway inflammation and the effect of melatonin in CS-induced COPD model mice and cigarette smoke extract (CSE)-stimulated MH-S cells. Our in vivo experiments revealed that melatonin treatment improved lung function and alleviated emphysema and airway inflammation in COPD mice. Additionally, elevated AM pyroptosis and increased NLRP3 inflammasome activation were observed in COPD mice, and both of these changes were mitigated by melatonin treatment. Further in vitro experiments demonstrated that melatonin inhibited NLRP3 inflammasome activation in MH-S cells. Importantly, melatonin also suppressed CSE-induced pyroptosis, as evidenced by improved membrane integrity (lower proportion of PI-positive cells and reduced LDH release), decreased levels of IL-1β and IL-18, and downregulated GSDMD-N expression. Notably, the NLRP3 inhibitor MCC950 reversed CSE-induced inflammation and pyroptosis, and the protective effect of melatonin was offset by treatment with the NLRP3 antagonist nigericin. Taken together, our results suggest that melatonin alleviates airway inflammation in COPD possibly by inhibiting NLRP3-mediated pyroptosis in AMs, thereby implicating AM pyroptosis in the pathogenesis of COPD and highlighting melatonin’s potential as a therapeutic candidate.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103305"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D mechanical stimulation modulates endothelial exosomes to promote fibroblast activation","authors":"Ye Qiu ,&nbsp;Zhenkun Lv ,&nbsp;Xingying Zhu ,&nbsp;Xiaoqian Yang ,&nbsp;Jiaming Wan","doi":"10.1016/j.tice.2026.103316","DOIUrl":"10.1016/j.tice.2026.103316","url":null,"abstract":"<div><h3>Background</h3><div>Mechanical forces play a crucial role in regulating cellular communication during tissue repair; however, it remains unclear how mechanical stimulation modulates endothelial exosome secretion and its effects on fibroblast activation.</div></div><div><h3>Methods</h3><div>In this study, endothelial cells were incorporated into 3D bioprinted tissue-engineered dermal constructs and cultured under static or mechanically stretched conditions. Exosomes were isolated from these cells, characterised, and applied to human dermal fibroblasts to assess their influence on proliferation, migration, and extracellular matrix formation. Data-independent acquisition proteomics was performed to analyse exosomal protein cargo and associated signalling pathways.</div></div><div><h3>Results</h3><div>Mechanical loading increased exosome secretion by approximately 2.5-fold without altering vesicle morphology. Functionally, mechanically stimulated exosomes enhanced fibroblast migration and type I collagen synthesis more significantly than controls. Proteomics profiling identified 4476 proteins in the exosomes, of which 677 were differentially expressed. Enrichment analysis revealed activation of the VEGF, HIF-1, Relaxin, and AGE–RAGE pathways, implicating roles in angiogenesis, metabolic regulation, and extracellular matrix remodelling.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate that 3D mechanical stimulation not only augments the quantity of endothelial exosomes but also reshapes their molecular cargo, thereby enhancing biomechanical communication between endothelial cells and fibroblasts. Building on prior evidence that fibroblast-derived exosomes promote endothelial angiogenesis, we propose a bidirectional ‘mechanical stimulation–exosome–communication–tissue reconstruction’ loop, providing a theoretical foundation for optimising exosome-based strategies in skin tissue engineering.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103316"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anatomical and microscopic evaluation of the liver in migratory shoveler ducks (Spatula clypeata): A multi-modal study using gross anatomy, vascular casting, morphometric analysis, and histochemistry techniques","authors":"Zeinab K. Aboghanima ,&nbsp;Ashraf El Sharaby ,&nbsp;Asmaa Aboelnour ,&nbsp;Mohamed M.A. Abumandour ,&nbsp;Ahmed G. Nomir","doi":"10.1016/j.tice.2026.103315","DOIUrl":"10.1016/j.tice.2026.103315","url":null,"abstract":"<div><div>This study was carried out to explore the anatomical and microscopic features of the liver in shoveler ducks using gross and vascular anatomical casting, morphometric analysis, and histochemical techniques. This study was applied to twenty-six adult ducks. The liver, located in the middle-third of the coelomic cavity, had a larger right lobe and no further subdivided lobes, housing the gallbladder in a cystic fossa on the right lobe's visceral surface. The liver’s venous drainage occurs through the hepatic veins (right, left, and middle) along with accessory and umbilical veins. The intrahepatic portal system consisted of two portal veins: left and right. Hepatic arterial supply originated from the celiac artery, which divided into right and left branches for intrahepatic distribution. The right branch gave dorsal and ventral right hepatic arteries and continued as the right gastric artery, while the left branch formed the left gastric artery and gave left hepatic arteries. Histologically, the liver was surrounded by a thick connective tissue (CT) capsule with poorly defined lobules and polygonal hepatocytes around central veins. Hepatocytes expanded toward the subscapular region with few fat globules within the cytoplasm, displaying a larger nucleus, and the sinusoids were filled with erythrocytes. Histochemical analysis revealed a strong positive reaction to the PAS stain. Densely packed collagen fibers were demonstrated by Masson's trichrome stain in the capsule, around large blood vessels, and bile ducts.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103315"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NFYA transcriptionally activates GPX4 inhibiting ferroptosis in colorectal cancer","authors":"Qingzhu Yang ,&nbsp;Shuo Sun ,&nbsp;Shuwei Dang ,&nbsp;Zeyan Li ,&nbsp;Lixue Feng ,&nbsp;Qiaoyi Yang ,&nbsp;Yanyan Sun ,&nbsp;Xin Huang ,&nbsp;Weiwei Zhang ,&nbsp;Zhicheng Zhang ,&nbsp;Guodong Li","doi":"10.1016/j.tice.2026.103325","DOIUrl":"10.1016/j.tice.2026.103325","url":null,"abstract":"<div><h3>Background</h3><div>Nuclear transcription factor Y subunit α (NFYA) has been reported to play functional roles in a range of malignancies, while its precise mechanistic function in the context of colorectal cancerer (CRC) progression has yet to be established.</div></div><div><h3>Methods</h3><div>TIMER2, UALCAN, and Kaplan-Meier Plotter databases were leveraged to evaluate the expression of NFYA and to gauge its prognostic relevance in CRC. Determine NFYA and glutathione peroxidase 4 (GPX4) expression in cell lines (NCM460, DLD1 and HCT116) and clinical samples using Quantitative Real-time PCR (qPCR) and western immunoblotting assay. Assessment of cell viability, proliferation, and migration involved MTT, EdU staining assay, colony formation, and flow cytometry. Malondialdehyde (MDA) content and lipid reactive oxygen species (ROS) levels were assessed using specialized kits. Mitochondrial ultrastructural changes were observed using transmission electron microscopy (TEM). The transcriptional regulation of GPX4 by NFYA was investigated through Luciferase reporter assays and Chromatin Immunoprecipitation Assay (ChIP) experiments.</div></div><div><h3>Results</h3><div>Higher levels of NFYA were expressed in CRC cells and clinical samples, and the upregulation of this target was associated with a worse prognostic outcome for patients with CRC. <em>In vitro</em>,the inhibition of NFYA expression impaired CRC cell proliferative and migratory activity. NFYA was found to function in part by binding to the GPX4 promoter and activating transcription, leading to an increase in GPX4 levels and consequent reductions in lipid peroxide levels and ferroptosis. NFYA binds to the promoter region of GPX4, regulating the transcription of GPX4. In the recovery experiment, inhibition of NFYA-induced ferroptosis in cells was reversed by GPX4. Correspondingly, the ferroptosis caused by GPX4 suppression can be reversed by NFYA.</div></div><div><h3>Conclusion</h3><div>NFYA is thus a promising target for therapies aimed at treating CRC. NFYA is a key regulator of ferroptosis resistance in CRC while also providing direct mechanistic insights into the oncogenic function that this protein plays in these tumor cells. NFYA/GPX4 may be one of the underlying reasons for malignant growth of CRC cells.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103325"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}