BMB Reports最新文献

{"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":"PPP1R3C functions as a tumor suppressor in endometrial cancer through promotion of glycogen synthesis.","authors":"Hyang Sook Seol, Jaewon Kim, Ju Hee Oh, Eunhye Choi, Sanghyuk Lee, Eun Ji Nam, Jaesang Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In this study, we report a novel function of protein phosphatase 1 regulatory subunit 3C (PPP1R3C)-which is known to promote glycogenesis by activating glycogen synthase and to inhibit glycogen breakdown by suppressing glycogen phosphorylase-as a tumor suppressor in endometrial cancer. First, the expression of PPP1R3C was strongly down-regulated in uterine corpus endometrial cancer (UCEC) tissues, and ectopic expression of PPP1R3C led to cell cycle arrest and apoptosis in HEC1A and HEC1B cells derived from UCEC. PPP1R3C also inhibited the growth of xenograft tumors in BALB/c nude mice. We found evidence indicating that the activation of glycogen synthesis was at least partly responsible for the tumor suppressor activity of PPP1R3C. Specifically, inhibition of glycogen synthase abrogated the effect of ectopic PPP1R3C expression on the growth inhibition of UCEC cells. Collectively, our data indicate that PPP1R3C is a tumor suppressor gene functioning through the induction of glycogen synthesis.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sperm as a multilayered epigenetic information system: encoding and transmission of paternal environmental signals.","authors":"Soonjoung Kim, Hye Yeon Lee, Seung Yong Kim, June-Yong Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Spermatozoa are increasingly recognized as carriers of non-genetic paternal information, rather than passive vehicles for the haploid genome. During spermatogenesis and post-testicular epididymal maturation, the paternal germline establishes a compact but functionally organized epigenome composed of DNA methylation, retained histones and histone modifications, chromatin-associated factors, and diverse small RNAs. These layers are environmentally responsive. In animal models, paternal diet, stress, toxicant exposure, and inflammatory or microbiome-related challenges can alter sperm DNA methylation, chromatin states, and small RNA cargo, with many changes mapping to loci involved in development, metabolism, and stress-response pathways. After fertilization, the paternal genome undergoes extensive epigenetic reprogramming; nevertheless, a subset of DNA methylation and chromatin features can resist erasure or be functionally relayed, while sperm-derived RNAs can influence early embryonic gene expression. Recent work, including studies of diet-induced sperm mitochondrial tRNAs, further supports the concept that defined paternal exposures may be transmitted to the embryo through discrete RNA-mediated mechanisms. In humans, lifestyle and environmental exposures are associated with measurable sperm epigenomic variation and with offspring health outcomes, but most evidence remains observational and is vulnerable to confounding by genetics, maternal factors, and shared environments. A central challenge is therefore to connect specific sperm epigenetic alterations to molecular effects in the early embryo and to subsequent offspring phenotypes. Here, we review how paternal environmental information is encoded during spermatogenesis and epididymal maturation, reshaped by environmental exposures, and interpreted by the early embryo, emphasizing multilayer integration and the evidence required to move from association to mechanism.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873013","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":"Single-cell multimodal analysis reveals enhancer and transcription factor regulatory dynamics during human iPSC-derived cardiomyocyte differentiation.","authors":"Hyejin Kim, Sun-Ho Lee, Chul Min Yang, Eun-Chong Lee, Ru-Ri Lee, Seunghyun Lee, Hyoung-Pyo Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes are widely used to model cardiac development and disease, but directed differentiation produces heterogeneous cellular states whose regulatory mechanisms remain incompletely defined. Here, we used simultaneous high-throughput ATAC and RNA Expression with sequencing (SHARE-seq) to profile gene expression and chromatin accessibility during human iPSC-derived cardiomyocyte differentiation. Weighted nearest neighbor integration resolved sequential developmental cell states, including iPSCs, mesodermal cells, progenitor populations, cardiomyocytes, and off-target, mixed, or partially differentiated populations. Peak-to-gene linkage analysis nominated cell state-associated putative enhancer-gene relationships, including a cardiac-related regulatory linkage at the MYH6/MYH7 locus. Pseudotime analysis revealed progressive remodeling of transcriptional and chromatin-associated regulatory programs. In silico perturbation modeling further prioritized transcription factors (TFs) predicted to influence differentiation trajectory progression, and gene regulatory network inference identified candidate TF-centered modules associated with cardiac lineage progression. Comparative pseudotime analysis of these modules showed that motif-containing regulatory element accessibility appeared to emerge earlier than, or in parallel with, TF expression and downstream target module activation. Together, these findings provide a single-cell multimodal resource and analytical framework for linking cellular identity, chromatin accessibility, putative enhancer-gene relationships, and candidate transcription factor regulatory programs during human cardiomyocyte differentiation.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872949","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":"FBXL18 activating AKT/CCND1 signaling pathway mediates radioresistance in esophageal squamous cell carcinoma.","authors":"Yahui Kang, Ning Ge, Xiaolong Yuan, Bihong Zhan, Hongbo Zhang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>F-box and leucine-rich repeat protein 18 (FBXL18) is closely associated with cancer progression. However, its role in regulating the radioresistance of esophageal squamous cell carcinoma (ESCC) remains unclear. Radioresistant ESCC cells were developed using fractional doses of X-ray irradiation, and validated via cell counting kit-8 (CCK-8) assay. The sensitivity of these radioresistant cells to radiotherapy was also assessed using CCK-8. The expression levels of FBXL18 and Cyclin D1 (CCND1) were analyzed through Western blotting. RNA interference (RNAi) technology was employed to investigate whether silencing FBXL18 could reduce ESCC radioresistance and inhibit the AKT/CCND1 signaling pathway. Co-immunoprecipitation and Western blotting were used to evaluate the polyubiquitination of AKT. Radioresistant ESCC cells were successfully established, and FBXL18 expression was significantly elevated in these cells. Increased levels of phosphorylated AKT (p-AKT) and CCND1 were also observed. Silencing FBXL18 notably reduced the radioresistance of ESCC cells and decreased p-AKT and CCND1 expression levels. Also, FBXL18 was found to interact with AKT, promoting its K63-linked polyubiquitination, and activating the AKT/CCND1 signaling pathway. FBXL18 interacts with AKT and facilitates its K63-linked polyubiquitination, thereby activating AKT/CCND1 signaling while maintaining the radioresistance of ESCC cells. [BMB Reports 2026; 59(9): 432-437].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"432-437"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141281","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}

{"title":"Multifaceted roles of KCTD17 in cellular homeostasis and disease.","authors":"Yelin Jeong, HyunJoon Gi, Young Hoon Jung, Ah-Reum Oh, Do-Wan Kim, Young Un Kim, Young Du Choi, KyeongJin Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Potassium channel tetramerization domain-containing protein 17 (KCTD17) is part of the BTB/POZ domain-containing KCTD protein family and serves as a multifunctional regulator of cellular homeostasis. As an adaptor protein associated with Cullin 3 (CUL3)-based E3 ubiquitin ligase complexes, KCTD17 plays a critical role in selective protein ubiquitination and proteasomal degradation, influencing the stability of various cellular proteins. This function links KCTD17 to numerous biological processes, including organelle dynamics, cell differentiation, intracellular signaling, metabolic regulation, stress responses, tissue remodeling, and disease progression. Notably, the effects of KCTD17 are highly context-dependent, varying with cell type, substrate availability, and pathological conditions. While recent studies have begun to uncover several pathways associated with KCTD17, its complete range of substrates, regulatory mechanisms, and physiological significance are still not fully understood. In this review, we summarize the current understanding of KCTD17's molecular functions and biological mechanisms, emphasizing its role as a proteostatic regulator. We also explore its potential relevance to human diseases and highlight key unresolved questions, such as substrate specificity, tissue-dependent functions, functional redundancy with related KCTD proteins, and therapeutic potential. Gaining a deeper understanding of KCTD17-dependent protein regulation may offer new insights into proteostasismediated cellular regulation and disease mechanisms. [BMB Reports 2026; 59(9): 418-424].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"418-424"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873030","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}

{"title":"APC/C-CDH1 suppresses AROS-mediated protection against DNA damage-induced senescence by ubiquitination.","authors":"Ji-Hye Yang, Hanbyeul Choi, Seung Baek Lee, Soo-Jong Um, Eun-Joo Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Anaphase-promoting complex/cyclosome (APC/C) regulates the cell cycle by destruction of target proteins ubiquitination. However, understanding the control of APC/C has remained elusive. We identify APC2, the catalytic core subunit of APC/C, as a binding partner of active regulator of SIRT1 (AROS). Subsequent immunoprecipitation assays confirm the interaction in vivo. We reveal that AROS competes with APC11 for APC2 binding, thereby impeding the destruction of Cyclin B1. By contrast, the APC/C coactivator CDH1 ubiquitinates and degrades AROS in a D-box-dependent manner. Finally, we demonstrate that CDH1 suppresses the AROS-mediated protection of DNA damage-induced senescence. Overall, our findings provide evidence of the reciprocal role of AROS and APC/C-CDH1 in regulating APC/C activity and DNA damage-induced senescence, and highlight a potential role for AROS in the control of senescence. [BMB Reports 2026; 59(9): 425-431].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"425-431"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013817","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}