Cell Biology and Toxicology最新文献

METTL3-driven m⁶A epigenetics in gastric cancer: unveiling oncogenic networks and clinical translation from tumorigenesis to therapy resistance. mettl3驱动的胃癌表观遗传学：揭示致癌网络和从肿瘤发生到治疗耐药的临床翻译。

IF 5.9 2区医学

Cell Biology and Toxicology Pub Date : 2025-09-26 DOI: 10.1007/s10565-025-10086-8

Xiaohong Fu, Xia Ruan, Jie He

{"title":"METTL3-driven m⁶A epigenetics in gastric cancer: unveiling oncogenic networks and clinical translation from tumorigenesis to therapy resistance.","authors":"Xiaohong Fu, Xia Ruan, Jie He","doi":"10.1007/s10565-025-10086-8","DOIUrl":"10.1007/s10565-025-10086-8","url":null,"abstract":"Globally, gastric cancer (GC) ranks among the deadliest malignancies due to frequent late-stage detection, metastatic dissemination, and resistance to therapies. Emerging evidence highlights N⁶-methyladenosine (m⁶A) modification, orchestrated by methyltransferase-like 3 (METTL3), as a pivotal epigenetic driver of GC pathogenesis. While METTL3 is implicated in promoting tumorigenesis, metastasis, and chemoresistance, a systematic synthesis of its multi-layered regulatory networks and clinical relevance remains elusive. This review comprehensively deciphers METTL3's dual roles as an oncogene and RNA modifier, elucidating its mechanisms in reprogramming GC progression through m⁶A-dependent RNA stability, translation, and non-coding RNA interactions. We reveal novel axes such as HOXA10-TGFβ /Smad-METTL3, METTL3/IGF2BP3-HDGF-glycolysis, and METTL3-YTHDF1- PARP1-driven chemoresistance, underscoring its cross-talk with oncogenic signaling and metabolic reprogramming. Crucially, we pioneer a clinical perspective by evaluating METTL3's diagnostic potential as a biomarker and its therapeutic vulnerability in immunotherapy and NSAID-based strategies. Our analysis identifies METTL3 as a central node in GC's molecular landscape, bridging epigenetic dysregulation with malignant phenotypes and therapy failure. These insights not only redefine METTL3's role in GC but also provide a roadmap for targeting m⁶A machinery in precision oncology.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"132"},"PeriodicalIF":5.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repeated exposure to CoCr28Mo6 particles leads to activation of NLRP3 inflammasome signaling in human osteoblasts. 重复暴露于CoCr28Mo6颗粒导致人成骨细胞NLRP3炎性体信号的激活。

IF 5.9 2区医学

Cell Biology and Toxicology Pub Date : 2025-09-23 DOI: 10.1007/s10565-025-10087-7

Marie-Luise Sellin, Luca Marit Koentopp, Rainer Bader, Anika Jonitz-Heincke

{"title":"Repeated exposure to CoCr28Mo6 particles leads to activation of NLRP3 inflammasome signaling in human osteoblasts.","authors":"Marie-Luise Sellin, Luca Marit Koentopp, Rainer Bader, Anika Jonitz-Heincke","doi":"10.1007/s10565-025-10087-7","DOIUrl":"10.1007/s10565-025-10087-7","url":null,"abstract":"Interleukin (IL)-1β and IL-18 are involved in the inflammatory response of wear-induced osteolysis. The production and secretion of these interleukins are regulated by the nucleotide-binding oligomerization domain leucine-rich repeat-containing protein (NLRP3) inflammasome. Uptake of wear particles can lead to mitochondrial damage, the production of reactive oxygen species (ROS), and stress in the endoplasmic reticulum (ER), resulting in an increased production of the ER stress key factor DNA damage-inducible transcript 3 (DDIT3). This factor is known to inhibit the mitophagy of dysfunctional mitochondria, inducing the generation of ROS. All these factors are known to activate the NLRP3 inflammasome. In this study, we investigated the influence of cobalt-chromium-molybdenum particles (CoCr) on the activation of the NLRP3 inflammasome in human osteoblasts (hOBs). Also, this research aimed to examine the impact of particles on mitochondria and the activation of the inflammasome. HOBs were primed with CoCr particles or tumor necrosis factor (TNF). After the incubation period, the cells were again treated with CoCr particles for activation. To test whether particle-induced DDIT3 upregulation has an effect on mitophagy and regulation of the NLRP3 inflammasome in hOBs, cells were additionally treated with the mitophagy agonist carbonyl cyanide-3-chlorophenylhydrazone (CCCP). Treatment of hOBs with metallic particles increased pyroptosis, which was accompanied by the release of IL-18. Further particle exposure damaged and inhibited the degradation of mitochondria. Activating the mitophagy with CCCP in hOBs reduced the inflammatory response to particles and TNF. These findings indicate that particle-induced inflammation can be influenced by maintaining mitochondrial function.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"131"},"PeriodicalIF":5.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SP1 and p23 play a crucial role in the circadian target gene induction of activated aryl hydrocarbon receptor in human breast cells. SP1和p23在人乳腺细胞活化芳烃受体的昼夜节律靶基因诱导中起关键作用。

IF 5.9 2区医学

Cell Biology and Toxicology Pub Date : 2025-09-12 DOI: 10.1007/s10565-025-10080-0

Melina Mihelakis, Tanina Flore, Gilbert Schönfelder, Michael Oelgeschläger, Norman Ertych

{"title":"SP1 and p23 play a crucial role in the circadian target gene induction of activated aryl hydrocarbon receptor in human breast cells.","authors":"Melina Mihelakis, Tanina Flore, Gilbert Schönfelder, Michael Oelgeschläger, Norman Ertych","doi":"10.1007/s10565-025-10080-0","DOIUrl":"10.1007/s10565-025-10080-0","url":null,"abstract":"The Aryl Hydrocarbon Receptor (AHR) is a crucial mediator of cellular responses upon exposure to environmental pollutants. Initially described as central activator in xenobiotic metabolism, recent research has unveiled additional layers of complexity in AHR function and regulation. The circadian rhythm is a fundamental regulatory process that modulates various physiological processes, including AHR activity. Our recent findings show that AHR-dependent gene induction is subject to circadian rhythmicity. While some studies suggest a circadian AHR gene transcription in various tissues, a comprehensive mechanistic understanding of the circadian AHR regulation remains elusive. This mechanistic study aimed to elucidate the circadian regulation of AHR target gene induction upon dioxin treatment in human breast cells. To acquire a more profound understanding of the intricacies of AHR regulation, we conducted a systematic analysis of the molecular co-factors and their interactions in circadian synchronized cells. Our results show circadian regulation of AHR transcriptional activity at the CYP1A1 promoter upon dioxin treatment. This appears to be orchestrated by the core clock components BMAL1/CLOCK, which directly interact with AHR in circadian synchronized cells. Additionally, we identified SP1 as an important positive and p23 as an essential negative regulator of circadian AHR activity. The understanding of these interactions is crucial for elucidating the molecular relationship between the circadian clock and cellular responses to environmental stimuli. Such knowledge is of vital importance for the application of New Approach Methods (NAMs) as part of a weight-of-evidence (WoE) approach in the next generation of risk assessments.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"130"},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12426158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Celastrol modulates IRS1 expression to alleviate ovarian aging and to enhance follicular development. Celastrol调节IRS1表达，缓解卵巢衰老，促进卵泡发育。

IF 5.9 2区医学

Cell Biology and Toxicology Pub Date : 2025-09-02 DOI: 10.1007/s10565-025-10079-7

Yao Jiang, Yonghua Shi, Meng Lv, Tao Wang, Penghao Wang, Xiaolong Yuan, Fei Gao, Bin Ma

{"title":"Celastrol modulates IRS1 expression to alleviate ovarian aging and to enhance follicular development.","authors":"Yao Jiang, Yonghua Shi, Meng Lv, Tao Wang, Penghao Wang, Xiaolong Yuan, Fei Gao, Bin Ma","doi":"10.1007/s10565-025-10079-7","DOIUrl":"10.1007/s10565-025-10079-7","url":null,"abstract":"Ovarian aging significantly contributes to the decline of the female reproductive system, adversely affecting fertility and endocrine homeostasis. To address the challenges posed by reproductive aging, natural products have shown promising preventive and therapeutic effects. Here, we investigated the beneficial effects of natural compound celastrol on ovarian development and aging, together with its underlying mechanisms. We found that celastrol administration at a concentration of 3 mg/kg promoted follicle development in young mice and enhanced porcine oocyte maturation, while regulating granulosa cell proliferation and apoptosis. In 12-month-old mice (equivalent to middle-aged adults), celastrol exhibited similar beneficial effects. Transcriptomic analysis revealed that differentially expressed genes post-celastrol treatment were associated with steroid biosynthesis, estrogen signaling pathways, type 2 diabetes, insulin secretion, meiosis, and apoptosis. Additionally, insulin receptor substrate 1 (IRS1), an adapter protein in insulin signaling, was shown to advance puberty in young mice and to facilitate oocyte maturation. Overexpression of IRS1 in oocytes promoted follicular development and oocyte maturation, resulting in enhanced steroid hormone levels, whereas IRS1 knockdown inhibited these processes. Our findings indicate that celastrol may regulate ovarian development and aging by modulating IRS1 expression and its related pathways, suggesting celastrol as a novel small-molecule compound targeting IRS1, and offering new perspectives for potential therapeutic strategies against reproductive aging and infertility.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"129"},"PeriodicalIF":5.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12405413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNMT1 recruits RUNX1 and represses FOXO1 transcription to inhibit anti-inflammatory activity of regulatory T cells and augments sepsis-induced lung injury. DNMT1招募RUNX1，抑制FOXO1转录，抑制调节性T细胞的抗炎活性，增强败血症诱导的肺损伤。

IF 5.9 2区医学

Cell Biology and Toxicology Pub Date : 2025-08-29 DOI: 10.1007/s10565-025-10069-9

Jurong Ding, Benyong Xu, Mingyan Wu, Mengling Zhan, Shanmei Wang, Haiwen Lu

{"title":"DNMT1 recruits RUNX1 and represses FOXO1 transcription to inhibit anti-inflammatory activity of regulatory T cells and augments sepsis-induced lung injury.","authors":"Jurong Ding, Benyong Xu, Mingyan Wu, Mengling Zhan, Shanmei Wang, Haiwen Lu","doi":"10.1007/s10565-025-10069-9","DOIUrl":"https://doi.org/10.1007/s10565-025-10069-9","url":null,"abstract":"Sepsis-induced lung injury (ALI) is a critical condition characterized by excessive immune responses and tissue damage. Previous evidence has underscored an upregulation pattern of DNA methyltransferase 1 (DNMT1) in sepsis. This study reveals the key role of DNMT1 in modulating regulatory T cell (Treg) activity in septic ALI. A septic mouse model was generated through cecal ligation and puncture. Treatment with either DNMT1 antagonist Thioguanine (ThG) or AAV-sh-DNMT1 significantly reduced immune cell infiltration, reduced production of pro-inflammatory cytokines, and increasing production of anti-inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of mice, alongside improved lung pathology and integrity. Furthermore, the DNMT1 inhibition or silencing significantly enhanced population of FOXP3+ Tregs in the BALF and lung tissue. Similar trends were observed in mice with specific DNMT1 deletion in CD4+ T cells (DNMT1-CD4-ko). Regarding the mechanism, we observed that DNMT1 represses transcription of forkhead box O1 (FOXO1) by recruiting RUNX family transcription factor 1 (RUNX1) to the FOXO1 promoter. FOXO1-specific knockout in CD4+ T cells reduced anti-inflammatory activity of Tregs. Additionally, administration of the CD25 antibody exacerbated sepsis-induced ALI in DNMT1-CD4-ko mice. Collectively, these findings illustrate that targeting DNMT1 interacts with RUNX1 to repress transcription of FOXO1, which reduces immunomodulatory activity of Tregs and augments inflammatory cascades in septic lung injury.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"128"},"PeriodicalIF":5.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: LINC00858 promotes colorectal cancer by sponging miR-4766-5p to regulate PAK2. 更正：LINC00858通过海绵miR-4766-5p调节PAK2促进结直肠癌。

IF 5.9 2区医学

Cell Biology and Toxicology Pub Date : 2025-08-25 DOI: 10.1007/s10565-025-10077-9

Wei Zhan, Xin Liao, Zhongsheng Chen, Lianghe Li, Tian Tian, Lei Yu, Rui Li

引用次数: 0

USP18 promotes ferroptosis in lipopolysaccharide-induced human kidney organoids by stabilizing STING1. USP18通过稳定STING1促进脂多糖诱导的人肾类器官铁下垂。

IF 5.9 2区医学

Cell Biology and Toxicology Pub Date : 2025-08-20 DOI: 10.1007/s10565-025-10078-8

Hao Yang, Lingfei Zhao, Weiwei Kong, Shanshan Liu, Qin Zhou, Xiabing Lang, Lan Lan, Yucheng Wang

{"title":"USP18 promotes ferroptosis in lipopolysaccharide-induced human kidney organoids by stabilizing STING1.","authors":"Hao Yang, Lingfei Zhao, Weiwei Kong, Shanshan Liu, Qin Zhou, Xiabing Lang, Lan Lan, Yucheng Wang","doi":"10.1007/s10565-025-10078-8","DOIUrl":"https://doi.org/10.1007/s10565-025-10078-8","url":null,"abstract":"Sepsis-induced acute kidney injury (SI-AKI) is a severe condition with limited therapeutic options, resulting in poor prognosis. Ferroptosis exacerbates the damage caused by SI-AKI, but the mechanisms regulating ferroptosis, especially those involving ubiquitination regulators, remain poorly understood. Here, we used a lipopolysaccharide (LPS)-induced human kidney organoid (HKO) model to investigate ferroptosis in SI-AKI. RNA sequencing (RNA-seq) analysis of control and LPS-treated HKOs revealed USP18 as the only upregulated ubiquitin-specific protease (USP) in response to LPS. Further investigations showed that depletion of USP18 significantly reduced ferroptosis in LPS-induced HKOs. To explore the mechanism underlying USP18's pro-ferroptotic role, we screened four ferroptosis-related drivers and identified STING1 as the key interacting protein with USP18. Mechanistically, USP18 directly binds to STING1, deubiquitinates it, and prevents its proteasomal degradation in HKOs. Overexpression of STING1 in USP18-deficient HKOs exacerbated ferroptosis, indicating that STING1 is crucial for mediating USP18's ferroptosis-promoting function in LPS-induced HKOs. Together, these findings establish that USP18-STING1 axis plays role in LPS-induced ferroptosis in HKOs, illuminating that targeting USP18-STING1 could provide neoteric therapeutic approach for treating SI-AKI.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"126"},"PeriodicalIF":5.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NAT10 Mediates Cardiac Fibrosis Induced by Myocardial Infarction Through ac4C Modification of TGFBR1 mRNA. NAT10通过ac4C修饰TGFBR1 mRNA介导心肌梗死诱导的心肌纤维化。

IF 5.9 2区医学

Cell Biology and Toxicology Pub Date : 2025-08-12 DOI: 10.1007/s10565-025-10081-z

Jiamin Zhou, Yu Chen, Jinfa Chen, Guojin Xia, Junyi Zeng, Liang Wang

{"title":"NAT10 Mediates Cardiac Fibrosis Induced by Myocardial Infarction Through ac4C Modification of TGFBR1 mRNA.","authors":"Jiamin Zhou, Yu Chen, Jinfa Chen, Guojin Xia, Junyi Zeng, Liang Wang","doi":"10.1007/s10565-025-10081-z","DOIUrl":"10.1007/s10565-025-10081-z","url":null,"abstract":"Cardiac fibrosis is a critical pathological process following myocardial infarction (MI), contributing to adverse cardiac remodeling and dysfunction. This study investigates the role of N-acetyltransferase 10 (NAT10), an RNA acetyltransferase, in mediating cardiac fibrosis through the N4-acetylcytidine (ac4C) modification of transforming growth factor beta receptor type 1 (TGFBR1) mRNA. Using a mouse model of MI, we demonstrated elevated levels of NAT10 and total ac4C RNA in left ventricular tissues, correlating with increased cardiac fibrosis. Echocardiographic analysis revealed significant impairment in cardiac contractile function, which was further validated by histological assessments using H&E and Masson staining. In vitro studies showed that TGF-β stimulation of cardiac fibroblasts led to enhanced NAT10 expression and myofibroblast differentiation, as evidenced by α-SMA staining. The role of NAT10 was further elucidated through fibroblast-specific knockout experiments, where the absence of NAT10 markedly attenuated cardiac fibrosis and improved echocardiographic parameters at eight weeks post-MI. Additionally, NAT10 knockout resulted in decreased mRNA and protein levels of fibrotic markers such as Collagen I and III, alongside reduced ac4C RNA modification. Additionally, we established that NAT10 enhances the stability of TGFBR1 mRNA via ac4C modification, as supported by RNA immunoprecipitation and luciferase assays. TGFBR1 overexpression countered the effects of NAT10 knockout, restoring fibrotic responses in both in vivo and in vitro models. These findings suggest that NAT10 plays a pivotal role in cardiac fibrosis following MI by regulating TGFBR1 mRNA stability through ac4C modification, thereby presenting potential therapeutic targets for mitigating cardiac fibrosis in post-MI patients.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"125"},"PeriodicalIF":5.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

METTL1 promotes cadmium-induced stress granules formation via enhancing translation of G3BP1 and expression of m⁷G- 3' tiRNA Met^CAT. METTL1通过增强G3BP1的翻译和m7G- 3' tiRNA MetCAT的表达来促进镉诱导的应激颗粒的形成。

IF 5.9 2区医学

Cell Biology and Toxicology Pub Date : 2025-08-05 DOI: 10.1007/s10565-025-10072-0

Wenyu Hu, Yaomin Liang, Xiaoling Ying, Yapeng Huang, Chang Xiong, Bixia Liu, Yifan Lv, Cong Chen, Chengcheng Zhang, Haiqing Zhang, Hu Li, Mei Yang, Weidong Ji

{"title":"METTL1 promotes cadmium-induced stress granules formation via enhancing translation of G3BP1 and expression of m7G- 3' tiRNA MetCAT.","authors":"Wenyu Hu, Yaomin Liang, Xiaoling Ying, Yapeng Huang, Chang Xiong, Bixia Liu, Yifan Lv, Cong Chen, Chengcheng Zhang, Haiqing Zhang, Hu Li, Mei Yang, Weidong Ji","doi":"10.1007/s10565-025-10072-0","DOIUrl":"10.1007/s10565-025-10072-0","url":null,"abstract":"Methyltransferase 1 (METTL1) is currently regarded as a key tRNA m7G writer. Recent studies indicate its potential role in carcinogenesis via increased m7G modification to stabilize tRNA and upregulate tRNA expression. Cadmium-induced stress triggers the assembly of stress granules (SGs) and production of tRNA-derived stress-induced RNAs (tiRNAs). However, whether METTL1 is involved in the formation of cadmium-induced SGs and its mechanism are still unclear. Here, we demonstrated that METTL1 promotes cadmium-induced SGs formation. Mechanistically, METTL1 not only upregulates SG's core protein Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) translation through tRNAs m7G modification, but also enhances expression of one m7G-modified tiRNA, m7G-3' tiRNA-MetCAT (mtiRM), which affects SGs assembly. Together, the findings concluded that the promotional effect of METTL1 on cadmium-induced SGs formation jointly through G3BP1 translation and mtiRM expression, thus providing insights into an intimate link between SGs and tumorigenesis.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"124"},"PeriodicalIF":5.9,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FTO-mediated the destabilization of RASGRF1 mRNA impedes thyroid cancer progression and suppresses macrophage M2 polarization. fto介导的RASGRF1 mRNA失稳阻碍甲状腺癌进展并抑制巨噬细胞M2极化。

IF 5.9 2区医学

Cell Biology and Toxicology Pub Date : 2025-08-04 DOI: 10.1007/s10565-025-10073-z

Zongyu Li, Jiancang Ma, Hao Guan, Jingyue Lai, Fangshi Xu, Gang Cao

{"title":"FTO-mediated the destabilization of RASGRF1 mRNA impedes thyroid cancer progression and suppresses macrophage M2 polarization.","authors":"Zongyu Li, Jiancang Ma, Hao Guan, Jingyue Lai, Fangshi Xu, Gang Cao","doi":"10.1007/s10565-025-10073-z","DOIUrl":"10.1007/s10565-025-10073-z","url":null,"abstract":"Background: The guanine nucleotide exchange factor RASGRF1 actively acts in a broad range of human cancers, including thyroid cancer (THCA). This study defined the activity of RASGRF1 in THCA progression and elucidated the m6A modification mechanism governing dysregulation of RASGRF1.Methods: Expression analyses were performed by immunoblotting, immunohistochemistry (IHC) or quantitative PCR. Cell growth was evaluated by colony formation and EdU proliferation assays. Animal experiments tested the function of RASGRF1 in xenograft growth. The conditioned medium (CM) of THCA cells was used to treat THP-1-differentiated macrophages. Cell apoptosis and CD206+ macrophages were assessed by flow cytometry. Cell invasiveness and migratory ability were detected by transwell assays. The influence of FTO in RASGRF1 was evaluated by RNA immunoprecipitation (RIP) and MeRIP assays.Results: RASGRF1 was upregulated in human THCA. RASGRF1 depletion retarded THCA cell growth, motility, invasiveness and promoted cell apoptosis and ferroptosis in vitro, as well as diminished the growth of TPC1 THCA xenograft tumors in vivo. Moreover, RASGRF1 depletion diminished M2 polarization and migration of THP-1-differentiated macrophages. Mechanistically, FTO reduced RASGRF1 mRNA stability via an m6A-dependent mechanism. FTO upregulation suppressed THCA malignant behaviors, promoted cell ferroptosis and reduced macrophage M2 polarization and migration through repression of RASGRF1.Conclusion: Our findings suggest that FTO-mediated the instability of RASGRF1 mRNA diminishes THCA-related macrophage M2 polarization and THCA progression. Anti-RASGRF1 strategies may be useful for the treatment of THCA.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"123"},"PeriodicalIF":5.9,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0