Biochimica et biophysica acta. Molecular basis of disease最新文献

{"title":"Rbm39 ameliorates metabolic dysfunction-associated steatotic liver disease by regulating Apob and Fabp4","authors":"Chunbo Zhuang ,&nbsp;Fangfang Cui ,&nbsp;Jin Chen ,&nbsp;Dezhi He ,&nbsp;Ting Sun ,&nbsp;Pei Wang","doi":"10.1016/j.bbadis.2025.167815","DOIUrl":"10.1016/j.bbadis.2025.167815","url":null,"abstract":"<div><div>Excessive hepatic lipid accumulation is the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), yet its underlying mechanisms still not fully understood. In this study, we identified RNA binding motif protein 39 (Rbm39) as a key modulator of hepatic lipid homeostasis during MASLD progression. To establish in vivo MASLD model, mice were fed either a high-fat diet (HFD) or a Gubra-Amylin NASH (GAN) diet. We employed adeno-associated virus to manipulate Rbm39 expression levels to assess its role in MASLD. Transcriptome analysis was conducted to pinpoint the genes targeted by Rbm39. Western blot, RT-PCR, dual-luciferase reporter gene assays, and alternative splicing analysis were utilized to delve into the molecular mechanisms. Our results showed that Rbm39 expression was notably decreased in the livers of MASLD mice. Knockdown of hepatic Rbm39 aggravated HFD-induced hepatic steatosis and GAN diet-induced MASH, along with a notable decrease in serum lipid levels. Conversely, overexpression of Rbm39 attenuated MASLD development and progression. RNA sequencing data analysis indicated that Rbm39 regulated the expression of apolipoprotein B (Apob) and fatty acid-binding protein 4 (Fabp4), both of which are crucial for lipid transport. Mechanistically, Rbm39 enhanced the transcription of Apob by upregulating hepatocyte nuclear factor 4α (Hnf4α), while it suppressed Fabp4 transcription by regulating alternative splicing of hypoxia inducible factor-1α (Hif-1α). These findings highlight the pivotal role of Rbm39 in maintaining hepatic lipid homeostasis and suggest its potential as a therapeutic target for MASLD.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167815"},"PeriodicalIF":4.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The RNA-binding protein LSM family regulating reproductive development via different RNA metabolism","authors":"Qin Chen,&nbsp;Ying Chen,&nbsp;Qingliang Zheng","doi":"10.1016/j.bbadis.2025.167808","DOIUrl":"10.1016/j.bbadis.2025.167808","url":null,"abstract":"<div><div>The LSM (Like-Sm) protein family, characterized by highly conserved LSM domains, is integral to ribonucleic acid (RNA) metabolism. Ubiquitously present in both eukaryotes and select prokaryotes, these proteins bind to RNA molecules with high specificity through their LSM domains. They can also form ring-shaped complexes with other proteins, thereby facilitating various fundamental cellular processes such as mRNA degradation, splicing, and ribosome biogenesis. LSM proteins play crucial roles in gametogenesis, early embryonic development, sex determination, gonadal maturation, and reproductive system formation. In pathological conditions, the absence of LSM14B leads to arrest of oocytes at mid-meiosis, downregulation of LSM4 expression is associated with abnormal spermatogenesis, and aberrant expression of LSM1 protein is linked to the occurrence and progression of breast cancer. This review focuses on the recent advances in the functional research of LSM proteins in reproduction.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167808"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Sorbs2 dysfunction on cardiovascular diseases","authors":"Xiaowei Xiong,&nbsp;Hon-Chi Lee,&nbsp;Tong Lu","doi":"10.1016/j.bbadis.2025.167813","DOIUrl":"10.1016/j.bbadis.2025.167813","url":null,"abstract":"<div><div>Despite significant advancements in prevention and treatment over the past decades, cardiovascular diseases (CVDs) remain the leading cause of death worldwide. CVDs involve multifactorial inheritance, but our understanding of the genetic impact on these diseases is still incomplete. Sorbin and SH3 domain-containing protein 2 (Sorbs2) is ubiquitously expressed in various tissues, including the cardiovascular system. Increasing evidence suggests that Sorbs2 malfunction contributes to CVDs. This manuscript will review our current understanding of the potential mechanisms underlying Sorbs2 dysregulation in the development of CVDs.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167813"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium-glucose cotransporter 2 inhibitor partially improves brain mitochondrial function, but does not mitigate cognitive impairment in rats with myocardial infarction","authors":"Nattayaporn Apaijai ,&nbsp;Tanawat Attachaipanich ,&nbsp;Chayodom Maneechote ,&nbsp;Hiranya Pintana ,&nbsp;Chanisa Thonusin ,&nbsp;Titikorn Chunchai ,&nbsp;Patcharapong Pantiya ,&nbsp;Busarin Arunsak ,&nbsp;Aphisek Kongkaew ,&nbsp;Nipon Chattipakorn ,&nbsp;Siriporn C. Chattipakorn","doi":"10.1016/j.bbadis.2025.167809","DOIUrl":"10.1016/j.bbadis.2025.167809","url":null,"abstract":"<div><div>Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are recommended to treat heart failure (HF) with the benefit of mitigating cognitive impairment in HF patients with type 2 diabetes. However, the underlying mechanisms are still unclear. This study aimed to investigate whether SGLT2i can improve cognitive function and synaptic plasticity in rats with myocardial infarction (MI) through attenuating inflammation, oxidative stress, impaired metabolism, and mitochondrial dysfunction in the brain. Male rats (<em>n</em> = 8/group) underwent either a sham operation or MI induced by permanent ligation of the left anterior descending coronary artery. MI rats with ejection fraction &lt;50 % were divided into three groups to receive either a vehicle, SGLT2i (Dapagliflozin, 1 mg/kg), or angiotensin-converting enzyme inhibitor (Enalapril, 10 mg/kg, positive control) for four weeks. Cardiac function, cognitive function, synaptic plasticity, dendritic spine density, and brain biochemical changes were assessed at the end of the protocol. MI rats exhibited cardiac dysfunction, hippocampal-dependent cognitive impairment, impaired synaptic plasticity, and loss of dendritic spines. Brain oxidative stress, inflammation, and mitochondrial dysfunction were also observed in MI rats. Treatment with SGLT2i and ACEi improved cardiac function but failed to attenuate cognitive impairment, synaptic dysplasticity, and loss of dendritic spine density in MI rats. A decrease in brain glutamate level was found following MI, which can be restored by SGLT2i and ACEi. Only SGLT2i partially improved brain mitochondrial function. In summary, SGLT2i enhanced glutamate levels and partially improved mitochondrial function in the brain; however, these changes were insufficient to improve cognitive function in MI rats.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167809"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial miR-34a deletion guards against aneurysm development despite endothelial dysfunction","authors":"Aleksandra Kopacz ,&nbsp;Damian Kloska ,&nbsp;Anna Bar ,&nbsp;Marta Targosz-Korecka ,&nbsp;Dominik Cysewski ,&nbsp;Kamil Awsiuk ,&nbsp;Aleksandra Piechota-Polanczyk ,&nbsp;Milena Cichon ,&nbsp;Stefan Chlopicki ,&nbsp;Alicja Jozkowicz ,&nbsp;Anna Grochot-Przeczek","doi":"10.1016/j.bbadis.2025.167812","DOIUrl":"10.1016/j.bbadis.2025.167812","url":null,"abstract":"<div><div>We previously reported a link between NRF2, a cytoprotective transcription factor, and the ageing of endothelial cells (ECs) and aorta. We also found that NRF2 KO mice are more susceptible to the development of abdominal aortic aneurysm (AAA), which is an age-associated condition. Since miR-34a is a marker of ageing, we explored its relationship with NRF2 and its role in vascular function and AAA formation.</div><div>Here, we demonstrate that premature NRF2-dependent ageing of ECs is mediated by miR-34a. Infusion of hypertensive angiotensin II (Ang II) in mice increases miR-34a in the aortic endothelial layer and serum, particularly in mice developing AAA. Mice lacking endothelial miR-34a exhibit severe EC dysfunction. Despite that, they are protected from AAA, also on the NRF2 KO background. This protective effect is reversed by rapamycin, which suppresses Ang II-induced EC proliferation. We identified MTA2, but not SIRT1, as a target of miR-34a that inhibits EC proliferation stimulated by Ang II. These findings suggest that fine-tuning of EC proliferation could have potential therapeutic implications for the treatment of aneurysms.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167812"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipidomics and cardiovascular disease","authors":"Arun Surendran ,&nbsp;Hannah Zhang ,&nbsp;Aleksandra Stamenkovic ,&nbsp;Amir Ravandi","doi":"10.1016/j.bbadis.2025.167806","DOIUrl":"10.1016/j.bbadis.2025.167806","url":null,"abstract":"<div><div>Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, necessitating innovative approaches for early detection and personalized interventions. Lipidomics, leveraging advanced mass spectrometry techniques, has become instrumental in deciphering lipid-mediated mechanisms in CVDs. This review explores the application of lipidomics in identifying biomarkers for myocardial infarction, heart failure, stroke, and calcific aortic valve stenosis (CAVS). This review examines the technological advancements in shotgun lipidomics and LC/MS, which provide unparalleled insights into lipid composition and function. Key lipid biomarkers, including ceramides and lysophospholipids, have been linked to disease progression and therapeutic outcomes. Integrating lipidomics with genomic and proteomic data reveals the molecular underpinnings of CVDs, enhancing risk prediction and intervention strategies. This review positions lipidomics as a transformative tool in reshaping cardiovascular research and clinical practice.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167806"},"PeriodicalIF":4.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glabridin ameliorates hemorrhagic shock induced acute kidney injury by activating Nrf2/HO-1 pathway","authors":"Lianghui Shu ,&nbsp;Zhe Zhang ,&nbsp;Nan Wang ,&nbsp;Qudong Yin ,&nbsp;Ya Chao ,&nbsp;Xin Ge","doi":"10.1016/j.bbadis.2025.167810","DOIUrl":"10.1016/j.bbadis.2025.167810","url":null,"abstract":"<div><div>Glabridin, a bioactive compound extracted from licorice, exhibits anti-inflammatory and antioxidative stress effects. It has rarely been reported in hemorrhagic shock (HS)-induced acute kidney injury (AKI). Here, the effects and potential mechanisms of Glabridin on HS-induced kidney injury was investigated. The active ingredient target network of licorice for HS-induced acute kidney injury was analyzed using network pharmacology. The study also examined the target gene-related biological processes and signaling pathways. To explore the impact of Glabridin on the kidney, a HS-induced rat model was established by femoral artery bleeding following tail vein injection of Glabridin. Glabridin improved kidney function evidenced by reduced levels of creatinine, urea nitrogen, neutrophil gelatinase-associated lipocalin in the serum, and the urinary protein/creatinine ratio in HS rats. This was inseparable from the inhibitory effect on apoptosis and kidney tubule injury. In addition, the protection of Glabridin on mitochondrial function was evident in the improvement of mitochondrial morphology, reduction of reactive oxygen species, increase in adenosine triphosphate, and upregulation of peroxisome proliferator-activated receptor γ coactivator 1-alph. These effects help reduce inflammation in kidney tissue. Hypoxia/reoxygenation-induced HK-2 cells were studied <em>in vitro</em>, and the same results were obtained in the cell model. Mechanically, Glabridin activated the Nrf2/HO-1 signaling pathway <em>in vivo</em> and <em>in vitro</em>, which may be a potential mechanism through which Glabridin protects kidney tissue. This study revealed the preventive effect of Glabridin on the kidney of HS rats, and provided insights for the development of Glabridin as a small molecule drug.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167810"},"PeriodicalIF":4.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple classes of human intracellular Heme-binding proteins with pathology-associated polymorphisms of heme coordinating residues","authors":"Stefanos A. Tsiftsoglou ,&nbsp;Asterios S. Tsiftsoglou","doi":"10.1016/j.bbadis.2025.167799","DOIUrl":"10.1016/j.bbadis.2025.167799","url":null,"abstract":"<div><div>Heme (Iron II-Protoporphyrin IX) is the pigment of life in all organisms and as a prosthetic group in vital hemoproteins contributes to pleiotropic molecular activities. In blood plasma, free heme is scavenged by hemopexin, albumin and several other proteins, while its biosynthesis, intracellular content and trafficking are normally monitored, and tightly regulated by an extensive network of diverse heme-binding proteins (HeBPs). The proteomic identification of numerous human HeBPs in recent studies prompted us to review, whether any of the identified HeBPs carry heme-binding motifs (HBMs) that exhibit genetic variations associated with pathologies. We improvised on a stepwise analytical methodology to identify HeBPs carrying disease-associated genetic (Single Nucleotide Polymorphisms-SNPs) and epigenetic (Post Translational Modifications-PTMs) variation within HBMs. Using the UniProt protein database, the HeMoQuest-WESA algorithms as well as the dbSNP, ClinVar and PhosphoSitePlus databases, we identified 1250 unique intracellular HeBPs containing 265 species with pathology-associated SNPs within putative HBMs. Among those, 136 exhibit pathology-associated polymorphisms in central heme coordinating residue positions of HBMs. We have noted over 15 protein classes of HeBPs with 377 encoded heme coordinating pathology polymorphisms, that based on population minor allele frequency (MAF) ratios, include 227 rare (&lt;1 % MAF) and 4 common (&gt;5 % MAF) variants. Among the latter is the cochaperone BAG3 rs2234962 that introduces the C151R substitution and varies considerably among populations. In addition, 3 more common variants were identified for the HeBPs CAST (rs754615), SERPINB8 (rs3826616) and DUOX2 (rs57659670). Also, 15 variants in 10 genes, including the Tyrosine-protein kinase ABL1 rs1060499547 (Y226C), introduce substitutions of Tyrosines (Y) normally phosphorylated. As substitutions and epigenetic marks can significantly alter the interactions of heme with HBMs, we propose that such variations can be associated with clinical pathologies.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167799"},"PeriodicalIF":4.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pannexin-2 deficiency disrupts visual pathways and leads to ocular defects in zebrafish","authors":"Riya Shanbhag ,&nbsp;Georg S.O. Zoidl ,&nbsp;Fatema Nakhuda ,&nbsp;Shiva Sabour ,&nbsp;Heike Naumann ,&nbsp;Christiane Zoidl ,&nbsp;Armin Bahl ,&nbsp;Nima Tabatabaei ,&nbsp;Georg R. Zoidl","doi":"10.1016/j.bbadis.2025.167807","DOIUrl":"10.1016/j.bbadis.2025.167807","url":null,"abstract":"<div><div>Pannexin-2 (Panx2) is a unique ion channel localized to ER-mitochondria contact sites. These specialized microdomains are abundant in neurons and glia and essential for cellular signaling and metabolism. While synaptic interactions are well-studied, the role of intracellular contacts, such as those of ER-mitochondrial junctions, in neuronal function and neurodegeneration remains largely unexplored. To investigate the roles of Panx2 in neuronal communication, we examined its expression pattern in the zebrafish brain and used TALEN technology to generate homozygous Panx2 knockout (<em>Panx2</em>^{<em>Δ11</em>}) zebrafish. Our results demonstrate that <em>panx2</em> mRNA is present in several brain regions, notably in visual centers such as the optic tectum and the thalamus. In 6 days post fertilization TL (<em>Panx2</em>^<em>+/+</em>) larvae, Panx2 expression was observed in the retina and the arborization fields of the optic tract. Transcriptome profiling of <em>Panx2</em>^{<em>Δ11</em>} larvae by RNA-seq analysis revealed down-regulation of genes involved in visual perception and lens development. Behavioral tests showed that loss of Panx2 leads to an altered ability to interpret visual information, such as changes in ambient illuminations, and respond with the characteristic motor action. Additionally, the knockout larvae displayed significantly impaired optomotor response. Lastly, when we tested the retinal structure of adult zebrafish eyes using optical coherence tomography, <em>Panx2</em>^{<em>Δ11</em>} fish revealed a longer mean axial length and a negative shift in retinal refractive error (RRE) values. Our findings highlight a distinct, novel function of Panx2 in sensory perception and ocular health, beyond its recognized roles in neurodevelopment and cancer.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167807"},"PeriodicalIF":4.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNF-α drives bladder cancer metastasis via METTL3-mediated m6A modification to promote CLASP2/IQGAP1-dependent cytoskeleton remodeling","authors":"Lingxiao Chen ,&nbsp;Cheng He ,&nbsp;Zhenyu Ou,&nbsp;Cheng Zhao","doi":"10.1016/j.bbadis.2025.167811","DOIUrl":"10.1016/j.bbadis.2025.167811","url":null,"abstract":"<div><h3>Background</h3><div>Bladder cancer (BCa) metastasis is a multi-step process triggered by cytoskeleton reorganization. However, the regulation mechanism of cytoskeleton reorganization in BCa remains ambiguous. This study elucidated the influence of tumor necrosis factor-alpha (TNF-α) in cytoskeleton remodeling during BCa metastasis and its possible mechanisms.</div></div><div><h3>Methods</h3><div>Colony formation, scratch, transwell, and the nude mouse model were adopted to evaluate the growth and metastasis. Molecular expression was assessed by immunohistochemical staining, quantitative real-time PCR (qRT-PCR), and Western blotting. The N6-methyladenosine (m6A) level was detected by methylated RNA immunoprecipitation (MeRIP). Protein interaction was validated by Co-immunoprecipitation (Co-IP). Immunofluorescence staining was used to identify rearrangement of actin filament fibers (F-actin) and protein colocalization.</div></div><div><h3>Results</h3><div>TNF-α facilitated cytoplasmic linker associated protein 2 (CLASP2) and methyltransferase like 3 (METTL3) expression in a dose (10–50 ng/mL)-dependent manner in BCa. CLASP2 high expression suggested a shorter overall survival of BCa patients. CLASP2 deficiency suppressed BCa cell proliferation, migration, and invasion via disrupting F-actin cytoskeleton. Mechanistically, TNF-α promoted METTL3-mediated m6A modification of CLASP2 to enhance CLASP2 mRNA stability. Moreover, CLASP2 directly interplayed with IQ motif containing GTPase activating protein 1 (IQGAP1) to regulate F-actin cytoskeleton remodeling. In vivo data demonstrated that inhibition of METTL3/CLASP2 axis delayed lung metastasis in nude mice.</div></div><div><h3>Conclusion</h3><div>TNF-α favors BCa cell metastasis, which involves METTL3-mediated m6A modification of CLASP2 that interacts with IQGAP1, thus leading to F-actin cytoskeleton remodeling. Our findings suggest targeting TNF-α/METTL3/CLASP2/IQGAP1 axis as a potential avenue for promising treatment for BCa.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 5","pages":"Article 167811"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}