BMB Reports最新文献

{"title":"Targeted inhibition of EGR1 by a KRAB-Linking Artificial Transcription Factor in A549 lung cancer cells.","authors":"Yena Choi, Euitaek Jung, Junekyu Han, Soon Young Shin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Transcription factors (TFs) are central regulators of gene expression, and engineered artificial TFs offer a programmable approach for modulating specific transcriptional programs. Early growth response 1 (EGR1) is an immediate-early zinc finger TF induced by inflammatory and growth signals and induces genes involved in proliferation, differentiation, and inflammation. In this study, we developed a KRAB-linked artificial transcriptional repressor by fusing the EGR1 zinc finger (ZnF) DNA-binding domain with the Krüppel-associated box (KRAB) repressor domain via a flexible linker (KRAB-Linker-EGR1 zinc finger; KLZ). KLZ localized predominantly in the nucleus and selectively bound to endogenous EGR1-binding sequences within the VCAM1 promoter, as demonstrated by DNA affinity precipitation and chromatin immunoprecipitation-quantitative PCR analyses. KLZ expression significantly suppressed IL-1β-induced VCAM-1 expression at both the mRNA and protein levels. KLZ inhibited cell migration and three-dimensional spheroid sprouting in A549 lung cancer cells. These findings demonstrated that KLZ effectively repressed EGR1-dependent transcription, highlighting its potential as a programmable artificial transcriptional repressor.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149317732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant cytokinin ortho-topolin riboside suppresses the proliferation of multiple myeloma cells by promoting β-catenin degradation.","authors":"Minji Kim, Wonku Kang, Sangtaek Oh","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Multiple myeloma involves the aberrant activation of the Wnt/β-catenin signaling pathway, resulting in β-catenin accumulation. Targeting this pathway presents a promising therapeutic approach for multiple myeloma. A cell-based chemical assay revealed that ortho-topolin riboside (oTR), a cytokinin naturally produced by Populus robusta, effectively suppressed the activation of β-catenin response transcription induced by Wnt3aconditioned medium. The mechanism underlying this suppression involved oTR-triggered phosphorylation of β-catenin at Ser33, Ser37, and Thr41, leading to its proteasomal degradation and a reduction in intracellular β-catenin levels. Furthermore, oTR consistently decreased β-catenin levels and inhibited the expression of Axin2, cyclin D1, and c-Myc-genes regulated by β-catenin/T cell factor signaling in multiple myeloma cells. Additionally, oTR inhibited the proliferation of multiple myeloma cells and promoted apoptosis, as evidenced by an increase in Annexin V-FITC-positive cells and elevated caspase-3/7 activity. These findings suggest that oTR exerts its antiproliferative effects by attenuating the Wnt/β-catenin pathway, indicating its potential as a therapeutic agent for preventing and treating multiple myeloma.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atorvastatin protects cardiomyocytes from doxorubicin toxicity by modulating YAP/TAZ signaling.","authors":"Heejung Lim, Suyeon Jin, Chan Joo Lee, Gibbeum Lim, Sungha Park, Sang-Hak Lee, Jaewon Oh, Seok-Min Kang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Doxorubicin (DOX) is a widely used anthracycline chemotherapeutic agent; however, its clinical efficacy is hampered by dose-dependent cardiotoxicity, which can lead to irreversible heart failure. Despite extensive research, effective strategies for preventing or mitigating DOX-induced cardiac injury remain lacking. The Hippo signaling effectors, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), are known to regulate cardiomyocyte survival, apoptosis, and mitochondrial quality control; however, their role in protecting the heart from DOX toxicity remains unclear. In this study, we investigated whether atorvastatin, a widely prescribed HMG-CoA reductase inhibitor with pleiotropic effects, attenuated DOX-induced cardiomyopathy by modulating the YAP/TAZ signaling axis. In H9c2 cardiomyocytes, DOX suppressed the expression of YAP and TAZ, leading to the downregulation of their downstream targets, Survivin and Park2, and activation of apoptotic cascades. Atorvastatin pretreatment restored YAP/TAZ expression at both mRNA and protein levels and reversed DOX-induced apoptosis. RNA interference-mediated knockdown of YAP or TAZ abolished the protective effects of atorvastatin, confirming the importance of this pathway. In a murine model of DOX cardiotoxicity, atorvastatin preserved left ventricular systolic function, reduced myocardial apoptosis and fibrosis, and restored YAP/TAZ, Survivin, and Park2 expression in the cardiac tissue. These findings suggest that atorvastatin exerts cardioprotective effects by restoring YAP/TAZ-mediated anti-apoptotic and mitochondrial quality control signaling. Our study highlights a novel mechanism via which atorvastatin mitigates DOX-induced cardiotoxicity and supports the therapeutic potential of YAP/TAZ modulation for cardioprotection.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"8-Chloro-cyclic AMP mediates growth inhibition of breast cancer cells via regulation of Yin-Yang 1 and estrogen receptor α levels.","authors":"Young Jun Cho, Ki Young Choi, Soo-Min Byeon, Soyeon Kim, Kyung-Hee Pyo, Tae Won Kim, Seung Hwan Hong, Jung Weon Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>As a derivative of cyclic AMP (cAMP), 8-Chloro-cyclic AMP (8-Cl-cAMP) is shown to induce growth inhibition, apoptosis, and differentiation in different cancer cells by activating AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK). The p38 MAPK is known as a downstream mediator of 8-Cl-cAMP and binds to a multifunctional transcription factor Yin-Yang 1 (YY1). Although cytotoxic effects of 8-Cl-cAMP on cancer cells have been studied over several decades, molecular details or interplays by which they allow selective cytotoxicity to certain cancer cells remain unclear. Here, we further examined how YY1 expression could be affected by 8-Cl-cAMP treatment to understand the mechanism involved in cytotoxic effects of 8-Cl-cAMP on breast cancer cells. Treatment with 8-Cl-cAMP significantly decreased YY1 levels. Such decrease was reversed by co-treatment with ABT702, an adenosine kinase inhibitor. Moreover, pre-treatment with Compound C, an AMPK inhibitor, restored 8-Cl-cAMP-mediated decrease of YY1 expression, whereas SB203580 (a p38 MAPK inhibitor) did not. Meanwhile, siRNA against YY1 caused phosphorylation of p38 MAPK but not of AMPK, resulting in cell growth inhibition and cell death, as did 8-Cl-cAMP. These in vitro results suggest that 8-Cl- cAMP-mediated cytotoxicity might involve downregulations of YY1, which functions downstream of AMPK and upstream of p38 MAPK, and of ERα levels, supporting AMPK-YY1-p38 MAPK signaling axis in response to 8-Cl-cAMP. This study also indicates that 8-Cl-cAMP may have therapeutic potential against breast cancers expressing YY1 and ERα.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Genes to Neural Circuits: Genetic and Systems Mechanisms of Ethanol Sensitivity and Tolerance in Drosophila melanogaster.","authors":"Abhimat Subedi, Youngseok Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Alcohol use disorder (AUD) is a complex neuropsychiatric disease shaped by genetic, environmental, and physiological factors. Over four decades, Drosophila melanogaster has emerged as a powerful model for dissecting the molecular and neural mechanisms underlying ethanol sensitivity, tolerance, preference, and consumption. Its conserved signaling pathways, sophisticated genetic toolkit, and robust behavioral assays have enabled discovery of genes and neural circuits governing alcohol responses across biological levels. This review summarizes major advances in the genetics and neurobiology of ethanol-related behaviors in Drosophila. Forward genetic screens identified conserved regulators of ethanol sensitivity and tolerance, including cAMP/PKA signaling components, ion channels, neurotransmitter receptors, cytoskeletal regulators, and neuropeptide pathways. Subsequent studies revealed distinct roles for the ellipsoid body, mushroom bodies, circadian neurons, and barrier glia in intoxication, tolerance, and reward. Epigenetic studies further established chromatin remodeling and transcriptional regulation as mechanisms of long-term behavioral plasticity, while systems genetics and genome-wide association studies highlighted the polygenic basis of natural variation in alcohol-related traits. Together, these findings advance an integrated view of ethanol action and provide a framework for understanding human AUD. Emerging approaches include single-cell and connectomics analyses, functional testing of human variants, and integration of systems genetics with circuit neuroscience.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inducible tristetraprolin suppresses malignant phenotypes and directly targets glucosaminyl (N-acetyl) transferase 3 in lung cancer cells.","authors":"Migyeong Kim, Eun Hui Jang, Seyeon Jung, Seung Jin Han, You-Soo Park, Si Ho Choi, Won-Tae Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tristetraprolin (TTP/ZFP36) regulates mRNA expression; however, its target genes in lung cancer remain unclear. Using a CRISPR/Cas9-engineered doxycycline-inducible TTP knock-in model in H460 cells, we investigated the function of TTP in lung cancer cells. Induced TTP expression suppressed clonogenicity, spheroid growth, proliferation, invasion, and migration. Transcriptomic analyses integrated with public lung adenocarcinoma datasets identified glucosaminyl (N-acetyl) transferase 3 (GCNT3) as a key effector of TTP in cancer progression. Mechanistic analyses indicated direct TTP binding to GCNT3, reducing its expression. GCNT3 knockdown attenuated invasion and migration, and GCNT3 re-expression in TTP-induced cells restored and further enhanced these malignant behaviors, establishing a functional relationship between TTP and GCNT3. Transient TTP expression in H1299 cells also reduced GCNT3 levels. These findings identify GCNT3 as a direct TTP target that contributes to malignant behaviors in lung cancer cells, providing insights into post-transcriptional regulation of tumor progression.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From heteroplasmy shift to direct base correction: mitochondrial genome editing for disease modeling and therapy.","authors":"Yerin Chi, Sung-Ik Cho","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mitochondria are essential organelles that support cellular energy metabolism and contribute broadly to tissue homeostasis, stress responses, and disease pathophysiology. As the mitochondrial genome encodes core components of oxidative phosphorylation, genetic alterations in mitochondrial DNA (mtDNA) can profoundly affect cellular and tissue function. Nevertheless, compared with the nuclear genome, mtDNA remains difficult to interrogate and manipulate because of longstanding technical barriers to mitochondrial genome engineering. Consequently, many fundamental questions surrounding mtDNA biology remain unresolved, including the mechanisms governing heteroplasmy, mutationspecific disease phenotypes, tissue-dependent pathogenic thresholds, and long-term mtDNA population dynamics. These limitations are particularly evident in mitochondrial genetic diseases, which can cause severe neurological, muscular, cardiac, and visual phenotypes but for which only a limited number of genetically defined disease models are available. Recent advances in mitochondrial genome editing are beginning to overcome these barriers. In this review, we organize the field according to therapeutic strategy, from selective depletion of mutant genomes to direct base correction and emerging precision-editing architectures. Mitochondria-targeted zinc-finger nucleases, mitoTALENs, and mitoARCUS can selectively eliminate mutant mtDNA and shift heteroplasmy toward wild-type genomes, whereas DddAderived cytosine base editors, TALE-linked deaminases, strandselective mitochondrial base editors, and their engineered derivatives enable direct C·G-to-T·A or A·T-to-G·C conversion without programmed double-strand breaks. We evaluate these platforms in relation to mutation class, heteroplasmy level, sequence context, bystander and off-target editing, target tissue, delivery format, durability, and functional rescue. Beyond therapeutic correction, mitochondrial genome editors are opening new opportunities for disease modeling by enabling defined pathogenic variants to be introduced into cells, organoids, and animal models. Validated applications include human cell and organoid systems and genetically defined mouse rat models. Extension to larger animals and nonhuman primates remains a future direction for the disease-modeling framework discussed here. Clinical translation, however, remains constrained by cargo size, co-delivery requirements, unintended nuclear exposure, long-term mtDNA dynamics, and the need for efficient and tissue-specific delivery to clinically relevant organs and cell types. Finally, we propose a framework linking genotype, heteroplasmy, and tissue context to editor selection, with the goal of moving the field from measurements of editing efficiency toward mechanistic understanding and therapeutic relevance.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-derived DLK1 restrains tumor progression through remodeling of the tumor immune microenvironment.","authors":"Yejin Lee, Hangyeol Park, Hyejin Min, Misu Kim, Seongwon Pak, So Young Park, Dong-Hoon Jeong, Dooil Jeoung, Keunwook Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The tumor immune microenvironment (TIME) plays a pivotal role in tumor progression and therapeutic responsiveness, yet the tumor-derived factors governing immune remodeling remain incompletely understood. Here, we identified delta-like homolog 1 (DLK1), a noncanonical Notch ligand, as a candidate regulator of the TIME through comparative transcriptomic analyses of murine tumors. DLK1 expression progressively declined during tumor progression and was inversely associated with tumor hypoxia. The hypoxia-responsive microRNA miR-338-5p contributed, at least in part, to the downregulation of DLK1 expression. Ectopic expression of DLK1 significantly suppressed the growth of B16 melanoma and LLC1 lung carcinoma tumors in syngeneic mice without substantially affecting tumor cell proliferation, apoptosis, or stem-like properties in vitro, consistent with a predominantly tumor cell-extrinsic mechanism. DLK1 expression was associated with immunostimulatory remodeling of the TIME, characterized by increased T cell infiltration and activation, reduced accumulation of myeloid-derived suppressor cells, and activation of tumor-associated macrophages toward an immunostimulatory phenotype. Consistently, recombinant DLK1-Fc directly enhanced macrophage activation and pro-inflammatory cytokine production in a contact-dependent manner. Collectively, our findings identify DLK1 as a previously unrecognized tumor-derived regulator of the TIME and suggest that hypoxia-driven loss of DLK1 may contribute to the establishment of an immunosuppressive microenvironment during tumor progression.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-translational control of synaptic adhesion molecules: molecular mechanisms and disease implications.","authors":"Seo-Young Yun, Ji-Hye Song, Kyung Ah Han","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Synaptic cell adhesion molecules (SAMs) are crucial for organizing synapse formation, maturation, and plasticity. No longer considered static structural links between pre- and postsynaptic membranes, SAMs are now understood to be dynamic signaling platforms whose functions are precisely controlled by various post-translational modifications (PTMs). For instance, conventional N- and O-linked glycosylation regulates protein folding and surface trafficking, whereas proteoglycan modification by heparan sulfate (HS) contributes to extracellular recognition and trans-synaptic interactions. Meanwhile, phosphorylation and dephosphorylation influence scaffold recruitment, synapse type specificity, and activity-dependent signaling. Additionally, proteolytic processing and ubiquitination manage the turnover, endocytosis, and signaling duration of adhesion complexes, allowing for rapid changes in synaptic connectivity. This review synthesizes recent progress on how these PTMs regulate SAMs and neurotrophin receptors across different scales, from individual synapses to entire neural circuits. We also discuss how PTM dysregulation contributes to neurodevelopmental and neuropsychiatric disorders and highlight the possibility that interactions among distinct PTMs may form a combinatorial regulatory code that further diversifies synaptic adhesion signaling, although this concept requires further investigation.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium: the protective cation singled out by Alzheimer's disease.","authors":"Seung Hyun Kim, Sun-Kyung Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Lithium is a mood stabilizer that is most prescribed in psychiatry for managing mental disorders. Many findings indicate that lithium is also neuroprotective in various neurodegenerative diseases. In particular, lithium has been of great interest as an affordable but still effective treatment for Alzheimer's disease (AD), due to its diverse neuroprotective actions and mechanistic overlap with key AD pathways, such as A production and tau modification. While the multifaceted activities may result from lithium's inhibitory action on two key enzymes, glycogen synthase kinase-3 beta (GSK-3) and inositol monophosphatase (IMPase), recent findings suggest that selective lithium depletion in neurons mediated by amyloid deposits may be a key pathological trigger in AD and supplementation with lithium orotate, a lithium salt with reduced amyloid binding, may even reverse brain damage and prevent cognitive decline. In this study, we review the neuroprotective properties of lithium, its known mechanisms of action, and discuss its therapeutic potential in AD, a topic that has been debated for decades. [BMB Reports 2026; 59(10): 456-465].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"456-465"},"PeriodicalIF":4.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13720688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}