Aixiang Lv, Meihuan Chen, Siwen Zhang, Wantong Zhao, Jingmin Li, Siyang Lin, Yanping Zheng, Na Lin, Liangpu Xu, Hailong Huang
{"title":"Upregulation of miR‑6747‑3p affects red blood cell lineage development and induces fetal hemoglobin expression by targeting BCL11A in β‑thalassemia.","authors":"Aixiang Lv, Meihuan Chen, Siwen Zhang, Wantong Zhao, Jingmin Li, Siyang Lin, Yanping Zheng, Na Lin, Liangpu Xu, Hailong Huang","doi":"10.3892/mmr.2024.13372","DOIUrl":"10.3892/mmr.2024.13372","url":null,"abstract":"<p><p>In β‑thalassemia, excessive α‑globin chain impedes the normal development of red blood cells resulting in anemia. Numerous miRNAs, including miR‑6747‑3p, are aberrantly expressed in β‑thalassemia major (β‑TM), but there are no reports on the mechanism of miR‑6747‑3p in regulating red blood cell lineage development and fetal hemoglobin (HbF) expression. In the present study, RT‑qPCR was utilized to confirm miR‑6747‑3p expression in patients with β‑TM and the healthy controls. Electrotransfection was employed to introduce the miR‑6747‑3p mimic and inhibitor in both HUDEP‑2 and K562 cells, and red blood cell lineage development was evaluated by CCK‑8 assay, flow cytometry, Wright‑Giemsa staining and Benzidine blue staining. B‑cell lymphoma/leukemia 11A (BCL11A) was selected as a candidate target gene of miR‑6747‑3p for further validation through FISH assay, dual luciferase assay and Western blotting. The results indicated that miR‑6747‑3p expression was notably higher in patients with β‑TM compared with healthy controls and was positively related to HbF levels. Functionally, miR‑6747‑3p overexpression resulted in the hindrance of cell proliferation, promotion of cell apoptosis, facilitation of cellular erythroid differentiation and γ‑globin expression in HUDEP‑2 and K562 cells. Mechanistically, miR‑6747‑3p could specifically bind to the 546‑552 loci of BCL11A 3'‑UTR and induce γ‑globin expression. These data indicate that upregulation of miR‑6747‑3p affects red blood cell lineage development and induces HbF expression by targeting BCL11A in β‑thalassemia, highlighting miR‑6747‑3p as a potential molecular target for β‑thalassemia therapy.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504401","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":"Osteosarcoma stem cells resist chemotherapy by maintaining mitochondrial dynamic stability via DRP1.","authors":"Boren Tian, Yaxuan Wu, Xiaoyun Du, Yan Zhang","doi":"10.3892/ijmm.2024.5451","DOIUrl":"10.3892/ijmm.2024.5451","url":null,"abstract":"<p><p>Osteosarcoma malignancy exhibits significant heterogeneity, comprising both osteosarcoma stem cells (OSCs) and non‑OSCs. OSCs demonstrate increased resistance to chemotherapy due to their distinctive cellular and molecular characteristics. Alterations in mitochondrial morphology and homeostasis may enhance chemoresistance by modulating metabolic and regulatory processes. However, the relationship between mitochondrial homeostasis and chemoresistance in OSCs remains to be elucidated. The present study employed high‑resolution microscopy to perform multi‑layered image reconstructions for a quantitative analysis of mitochondrial morphology. The results indicated that OSCs exhibited larger mitochondria in comparison with non‑OSCs. Furthermore, treatment of OSCs with cisplatin (CIS) or doxorubicin (DOX) resulted in preserved mitochondrial morphological stability, which was not observed in non‑OSCs. This finding suggested a potential association between mitochondrial homeostasis and chemoresistance. Further analysis indicated that dynamin‑related protein 1 (DRP1) might play a pivotal role in maintaining the stability of mitochondrial homeostasis in OSCs. Depletion of DRP1 resulted in the disruption of mitochondrial stability when OSCs were treated with CIS or DOX. Additionally, knocking out DRP1 in OSCs led to a reduction in chemoresistance. These findings unveil a novel mechanism underlying chemoresistance in osteosarcoma and suggest that targeting DRP1 could be a promising therapeutic strategy to overcome chemoresistance in OSCs. This provided valuable insights for enhancing treatment outcomes among patients with osteosarcoma.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604496","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}
Oncology reportsPub Date : 2025-01-01Epub Date: 2024-11-08DOI: 10.3892/or.2024.8835
Ok-Hyeon Kim, Israt Jahan Tulip, Hana Kang, Eun Seo Chang, Hyun Jung Lee
{"title":"Compression force promotes glioblastoma progression through the Piezo1‑GDF15‑CTLA4 axis.","authors":"Ok-Hyeon Kim, Israt Jahan Tulip, Hana Kang, Eun Seo Chang, Hyun Jung Lee","doi":"10.3892/or.2024.8835","DOIUrl":"10.3892/or.2024.8835","url":null,"abstract":"<p><p>Glioma, a type of brain tumor, is influenced by mechanical forces in its microenvironment that affect cancer progression. However, our understanding of the contribution of compression and its associated mechanisms remains limited. The objective of the present study was to create an environment in which human brain glioma H4 cells experience pressure and thereby investigate the compressive mechanosensors and signaling pathways. Subsequent time‑lapse imaging and wound healing assays confirmed that 12 h of compression significantly increased cell migration, thereby linking compression with enhanced cell motility. Compression upregulated the expression of Piezo1, a mechanosensitive ion channel, and growth differentiation factor 15 (GDF15), a TGF‑β superfamily member. Knockdown experiments targeting <i>PIEZO1</i> or <i>GDF15</i> using small interfering RNA resulted in reduced cell motility, with Piezo1 regulating GDF15 expression. Compression also upregulated CTLA4, a critical immune checkpoint protein. The findings of the present study therefore suggest that compression enhances glioma progression by stimulating Piezo1, promoting GDF15 expression and increasing CTLA4 expression. Thus, these findings provide important insights into the influence of mechanical compression on glioma progression and highlight the involvement of the Piezo1‑GDF15 signaling pathway. Understanding tumor responses to mechanical forces in the brain microenvironment may guide the development of targeted therapeutic strategies to mitigate tumor progression and improve patient outcomes.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"53 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605781","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}
AssessmentPub Date : 2025-01-01Epub Date: 2024-03-29DOI: 10.1177/10731911241239772
Ahmed Kerriche
{"title":"Psychometric Evaluation of the Social Phobia Inventory (SPIN) in Algeria: A Comprehensive Approach Utilizing Network Analysis, Confirmatory Factor Analysis, and the Polytomous Rasch Model.","authors":"Ahmed Kerriche","doi":"10.1177/10731911241239772","DOIUrl":"10.1177/10731911241239772","url":null,"abstract":"<p><p>This study aimed to evaluate the psychometric characteristics of the Social Phobia Inventory (SPIN) by employing network analysis, confirmatory factor analysis, and the Polytomous Rasch Model. A cross-sectional data set was collected comprising 1,530 participants, with 959 being women and 571 being men. The Bootstrap Exploratory Graph Analysis unveiled the presence of two dimensions, with Items 17, 15, 5, 14, 6, and 9 exhibiting the highest strength centrality index. Notably, the Network Comparison Test indicated no differences in Network Invariance and global strength between the networks of women and men. Furthermore, the confirmatory factor analysis results demonstrated that the two extracted dimensions displayed an acceptable goodness of fit. In addition, the reliability coefficient values were acceptable, exceeding the threshold of 0.70. The Rasch analysis results suggested an overall fit, but some items exhibited overlap, suggesting their potential removal. Furthermore, it was recommended to develop new items to address gaps between existing items, particularly for measuring the lower levels of Social Anxiety Disorder. In conclusion, these findings provide robust evidence supporting the reliability and validity of the SPIN as a tool for measuring Social Anxiety Disorder in Algeria.</p>","PeriodicalId":8577,"journal":{"name":"Assessment","volume":" ","pages":"147-161"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140326310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Baicalein suppresses inflammation and attenuates acute lung injury by inhibiting glycolysis via HIF‑1α signaling.","authors":"Zhongyou Liu, Xiaona Zheng, Ning Li, Zongyao Wang","doi":"10.3892/mmr.2024.13383","DOIUrl":"10.3892/mmr.2024.13383","url":null,"abstract":"<p><p>Baicalein, a flavonoid monomer compound isolated from the dried root of the traditional Chinese herb <i>Scutellaria baicalensis</i>, has several pharmacological activities, such as anti‑inflammatory, anti‑angiogenic, antitumor, antimicrobial and antiviral properties. Acute lung injury (ALI) is characterized by injury of the alveolar epithelium and capillary endothelium, which results in decreased lung volume, decreased lung compliance, ventilation/perfusion mismatch, intrapulmonary edema, alveolar edema and even acute hypoxemic respiratory failure. The present study aimed to investigate the effects of baicalein on lung injury and inflammation. Bioinformatics analysis using network pharmacology predicted that the hypoxia inducible factor‑1α (HIF‑1α) and glycolysis signaling pathways were involved in the mechanism underlying the therapeutic effects of baicalein. Further <i>in vitro</i> and <i>in vivo</i> experiments, such as immunohistochemistry, immunofluorescence and PCR, verified that baicalein could inhibit HIF‑1α signaling, thus suppressing glycolysis, and improving inflammatory responses and ALI. Taken together, the results of the present study suggested that the anti‑inflammatory effects of baicalein on treating ALI were associated with its ability to suppress glycolysis via the HIF‑1α signaling pathway.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603307","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":"Enocyanin promotes osteogenesis and bone regeneration by inhibiting MMP9.","authors":"Wei Mao, Yinfeng Zheng, Wencong Zhang, Jinrong Yin, Zhiyi Liu, Peiliang He, Guodong Hou, Guowei Huang, Huan Chen, Junyan Lin, Jiake Xu, Aiguo Li, Shengnan Qin","doi":"10.3892/ijmm.2024.5450","DOIUrl":"10.3892/ijmm.2024.5450","url":null,"abstract":"<p><p>Enocyanin (ENO), an anthocyanin extracted from grapes, has been shown to exert inhibitory effects on acid phosphatase and inflammation; however, its role in osteogenesis and bone formation is currently unknown. The present study aimed to investigate the effects of ENO on osteogenesis <i>in vitro</i> and bone formation <i>in vivo</i>, and to explore the rudimentary mechanisms. KusaO cells were employed to evaluate the osteogenic role of ENO <i>in vitro</i> by Alizarin red S staining, ALP staining, quantitative PCR and western blotting, and an <i>in vivo</i> analysis of the therapeutic effects of ENO on a femoral fracture model was performed using stereo microscope, micro‑CT and histological staining. To further investigate the underlying mechanisms, mRNA sequencing was employed to investigate the changes in gene expression and the downstream pathways after ENO treatment. The results showed that ENO could promote the osteogenic differentiation of KusaO cells <i>in vitro</i> and bone fracture regeneration <i>in vivo</i>. Mechanistically, ENO was highly related to bone formation, including the 'Wnt signalling pathway', 'bone development' and 'bone mineralization'. In addition, matrix metalloproteinase 9 (MMP9) was identified as one of the targets of ENO in its promotional role in osteogenesis. In conclusion, ENO may represent a therapeutic candidate for bone regeneration in bone fractures by regulating osteogenesis and bone formation via MMP9.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604488","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}
Lin Ma, Xia Kang, Jindong Tan, Yunjiao Wang, Xiao Liu, Hong Tang, Lin Guo, Kanglai Tang, Xuting Bian
{"title":"Denervation‑induced NRG3 aggravates muscle heterotopic ossification via the ErbB4/PI3K/Akt signaling pathway.","authors":"Lin Ma, Xia Kang, Jindong Tan, Yunjiao Wang, Xiao Liu, Hong Tang, Lin Guo, Kanglai Tang, Xuting Bian","doi":"10.3892/mmr.2024.13374","DOIUrl":"10.3892/mmr.2024.13374","url":null,"abstract":"<p><p>Peripheral nerve injury exacerbates progression of muscle heterotopic ossification (HO) and induces changes in expression of local cytokines in muscle tissue. The objective of the present study was to assess the impact of peripheral nerve injury on muscle HO development and the mechanism of cytokine modulation. A mouse model of gastrocnemius muscle HO was established and the sciatic nerve cut to simulate peripheral nerve injury. To evaluate the underlying factors contributing to the exacerbation of muscle HO resulting from denervation, fresh muscle tissue was collected and micro‑computed tomography, histochemical staining, RNA‑sequencing, reverse transcription‑quantitative PCR, Western blot, muscle tissue chip array were performed to analyze the molecular mechanisms. Sciatic nerve injury exacerbated HO in the gastrocnemius muscle of mice. Moreover the osteogenic differentiation of nerve‑injured muscle tissue‑derived fibro‑adipogenic progenitors (FAPs) increased <i>in vitro</i>. The expression of neuregulin 3 (NRG3) was demonstrated to be increased after nerve injury by muscle tissue chip array. Subsequent transcriptome sequencing analysis of muscle tissue revealed an enrichment of the PI3K/Akt pathway following nerve injury and an inhibitor of the PI3K/Akt pathway reduced the osteogenic differentiation of FAPs. Mechanistically, <i>in vitro</i>, peripheral nerve injury increased secretion of NRG3, which, following binding to ErbB4 on the cell surface of FAPs, promoted expression of osteogenesis‑associated genes via the PI3K/Akt signaling pathway, thus contributing to osteogenic differentiation of FAPs. <i>In</i> <i>vivo</i>, inhibition of the PI3K/Akt pathway effectively protected against muscle HO induced by peripheral nerve injury in mice. The present study demonstrated that the regulatory roles of NRG3 and the PI3K/Akt pathway in peripheral nerve injury exacerbated muscle HO and highlights a potential therapeutic intervention for treatment of peripheral nerve injury‑induced muscle HO.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504396","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}
Oncology reportsPub Date : 2025-01-01Epub Date: 2024-11-08DOI: 10.3892/or.2024.8834
Mei Wang, Xu Chen, Guang Fu, Mingjian Ge
{"title":"[Retracted] Glutathione peroxidase 2 overexpression promotes malignant progression and cisplatin resistance of KRAS‑mutated lung cancer cells.","authors":"Mei Wang, Xu Chen, Guang Fu, Mingjian Ge","doi":"10.3892/or.2024.8834","DOIUrl":"10.3892/or.2024.8834","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the BrdU incorporation assay data shown in Fig. 7C were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Lu M, Qin X, Zhou Y, Li G, Liu Z, Geng X and Yue H: Long non‑coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR‑424‑5p/BCL9L axis. Cell Death Dis 12: 72, 2021]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to <i>Oncology Reports</i>, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 48: 207, 2022; DOI: 10.3892/or.2022.8422].</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"53 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605770","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}
Oncology reportsPub Date : 2025-01-01Epub Date: 2024-11-08DOI: 10.3892/or.2024.8836
Guiyu Zhang, Xinxin Hou, Shuhong Gao
{"title":"[Retracted] Stimulation of peroxisome proliferator‑activated receptor γ inhibits estrogen receptor α transcriptional activity in endometrial carcinoma cells.","authors":"Guiyu Zhang, Xinxin Hou, Shuhong Gao","doi":"10.3892/or.2024.8836","DOIUrl":"10.3892/or.2024.8836","url":null,"abstract":"<p><p>Following the publication of this paper, after having performed an independent analysis of the data shown in the various of the figures in the Editorial Office, it was identified that, in Fig. 5A and B on p. 1232 showing the results of Transwell invasion and migration experiments, the majority of the data panels exhibited overlapping sections of data, such that the affected panels, which were intended to show the results of differently performed experiments, had all apparently been derived from the same original sources. Owing to the large number of duplications of data that have been identified in this paper, the Editor of <i>Oncology Reports</i> has decided that it should be retracted from the Journal on account of a lack of confidence in the presented data. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 33: 1227‑1234, 2015; DOI: 10.3892/or.2015.3729].</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"53 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605775","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":"4‑Methoxydalbergione inhibits the tumorigenesis and metastasis of lung cancer through promoting ferroptosis via the DNMT1/system Xc‑/GPX4 pathway.","authors":"Jun Fan, Haoran Lin, Jinhua Luo, Liang Chen","doi":"10.3892/mmr.2024.13384","DOIUrl":"10.3892/mmr.2024.13384","url":null,"abstract":"<p><p>Lung cancer is responsible for the highest number of tumor‑related deaths worldwide. A flavonoid extracted from the heartwood of <i>Dalbergia sissoo</i> Roxb., 4‑methoxydalbergione (4‑MD), exhibits potent anticancer activity in multiple malignancies; however, the potential anticancer activity of 4‑MD in lung cancer has not yet been elucidated. In the present study, A549 cells were treated with increasing concentrations of 4‑MD, and cell viability was assessed using a Cell Counting Kit‑8 assay. In addition, colony formation, 5‑ethynyl‑2'‑deoxyuridine, wound healing and Transwell assays were conducted to evaluate cell proliferation, migration and invasion, respectively. Cell morphology was observed using transmission electron microscopy, and ferroptosis was determined using thiobarbituric acid reactive substance, lipid reactive oxygen species (ROS) and iron assays. Moreover, molecular docking was used to verify the potential interaction between 4‑MD and DNA methyltransferase 1 (DNMT1). Tumor‑bearing mice were established and treated with 10 or 30 mg/kg 4‑MD, and tumor volume and weight were recorded. Immunohistochemistry and Prussian blue staining were conducted to examine Ki‑67 expression and iron deposition in tumor tissues, and protein expression was further explored using western blot analysis. The results of the present study revealed that 4‑MD significantly inhibited cell proliferation, migration, invasion and epithelial‑mesenchymal transition in a concentration‑dependent manner. Notably, 4‑MD induced ferroptosis via increased lipid peroxidation, lipid ROS and Fe2+ levels. In addition, it was revealed that 4‑MD can directly bind to DNMT1 to inhibit expression, and inhibit solute carrier family 7 member 11 (SLC7A11; also known as cystine‑glutamate antiporter) and glutathione peroxidase 4 expression. Following DNMT1 overexpression, the observed antitumor activity and ferroptosis‑promoting effects of 4‑MD were partially reversed. Furthermore, 4‑MD significantly inhibited tumor growth <i>in vivo</i>, and reduced tumor volume and weight. In addition, Ki‑67 expression was reduced while iron deposition was increased in the tumor tissues of mice following treatment with 4‑MD. In conclusion, 4‑MD may exhibit anticancer activity through the promotion of DNMT1‑mediated cell ferroptosis. Thus, 4‑MD may have potential as a novel therapeutic agent in the treatment of lung cancer.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603302","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}