BMB Reports最新文献

{"title":"Tumor subtype-specific transcriptional signatures predict recurrence risk in hepatocellular carcinoma.","authors":"Hyeran Shim, Hoang Bao Khanh Chu, Jiun Kim, Seohyeon Park, Subin Yoo, Jeongsil Kim-Ha, Young-Joon Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) displays significant molecular heterogeneity that clinical staging alone does not fully account for when assessing the risk of recurrence following curative treatment. To address this, we developed a multi-cohort survival modeling framework that translates bulk RNA-seq profiles into biologically meaningful tumor lineage scores. These scores are then used to stratify disease-free survival (DFS). Our study included 1,059 patients from four independent cohorts, where tumor immunogenic and proliferative lineage scores satisfied the proportional hazards assumptions and were integrated into a cohort-stratified Cox model. Each patient received a linear predictor (LP), and predefined cutpoints were established to categorize them into actionable risk groups. These groups exhibited consistent DFS separation in both the training (70%) and independent test (30%) sets. In ROC analyses, the LP demonstrated moderate overall discrimination (AUC 0.629, 95% CI 0.595-0.662). It showed higher discrimination for early recurrence (＜ 1 year; AUC 0.653, 95% CI 0.591-0.715) and lower discrimination for later recurrence (3-5 years; AUC 0.576, 95% CI 0.473-0.678). This approach establishes a biologically informed framework for stratifying recurrence risk based on RNA-seq data, potentially enhancing riskadapted surveillance and postoperative management for HCC. [BMB Reports 2026; 59(9): 438-442].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"438-442"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663243","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":"Alzheimer's disease through the lens of mesenchymal drift: the collapse of cellular identity.","authors":"Juyeong Jeon, Jichang Yu, Sung Bae Lee, Jinsoo Seo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cellular identity is maintained by precise epigenetic regulation, but chronic stress and aging can disrupt this control, leading to mesenchymal drift (MD). Unlike the coordinated process of epithelial-mesenchymal transition (EMT), MD is a stochastic, lineage-independent phenomenon marked by increased epigenetic noise and the widespread activation of profibrotic gene programs. As originally defined, MD requires two components to co-occur: a compromised original cellular identity together with the acquisition or intensification of mesenchymal traits. Applying the MD framework to Alzheimer's disease (AD) provides a new perspective on its pathogenesis. In AD, brain cells do not merely survive or die due to protein toxicity; instead, they lose their specialized identities in an uncoordinated fashion. This transcriptomic drift has been reported across major cell types in the central nervous system: neural progenitor cells differentiate prematurely, mature neurons undergo transcriptomic dedifferentiation, endothelial cells develop features of vascular fibrosis, and glial cells lose their homeostatic functions. Direct enrichment of the MD signature in the AD brain, however, has so far been demonstrated only in astrocytes, oligodendrocytes, and pericytes, and, in our own reanalysis, in human-induced pluripotent stem cell (hiPSC)-derived neural progenitor cells carrying an APP mutation; we distinguish this evidence from observations documenting identity loss or a reactive state alone. We further caution that the novel cell populations identified in recent single-cell transcriptomic studies should not be assumed to represent genuinely new cell types: such clusters may equally reflect a blurring of existing cell lineages, or technical artifacts that produce the same appearance. A drifting transcriptomic profile also does not always signify a corresponding physiological change. These possibilities warrant careful attention, and we therefore emphasize the critical need to integrate transcriptomic data with in vivo functional and morphological validation. This integration is essential to determine whether these identity shifts contribute to AD progression or merely reflect underlying epigenetic instability. [BMB Reports 2026; 59(9): 407-417].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"407-417"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873008","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":"T cell-based immunotherapy in solid tumors: mechanistic barriers and emerging opportunities.","authors":"Hojin Chun, Hyunjin Ju, Sung-Min Hwang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>T cell-based immunotherapies have transformed the treatment of hematological malignancies, but their efficacy in solid tumors remains inconsistent. Unlike blood cancers, solid tumors present multiple barriers that impede T cell infiltration, metabolic fitness, antigen recognition, and long-term persistence. These barriers include structural exclusion by the stroma, tumor-driven metabolic competition, antigen plasticity, and the progressive epigenetic fixation of T cell exhaustion states. This review integrates our current understanding of T celldirected therapeutic approaches and examines the tumorintrinsic and microenvironmental mechanisms that limit their activity in solid malignancies. We discuss how chronic stress signaling, altered nutrient availability, glycan-mediated epitope masking, and transcriptional reprogramming collectively destabilize therapeutic T cell function. Finally, we evaluate emerging strategies designed to remodel the tumor niche, diversify antigen targeting, and enhance T cell metabolic and epigenetic resilience. Thus, developing a mechanistic framework that combines intrinsic T cell reprogramming with adaptation to the tumor context will be crucial for extending durable T cell-mediated immunity to solid cancers.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663259","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":"Galectin-3 Negatively Regulates miR-31 Processing in Breast Cancer Cells.","authors":"Gi Soo Youn, Woo Young Lim, Yubin Kim, Soeun Lee, Jonghwan Choi, Yoon Shin Cho, Hyo Jeong Kuh, Jong Kook Park","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>MicroRNA-31 (miR-31) acts as a tumor suppressor and is downregulated in breast cancer, but the mechanism responsible for its reduced maturation remains unclear. To investigate this, we examined the expression patterns of pri- and mature miR-31 across multiple human tumor cell lines. Quantitative PCR revealed that while pri-miR-31 was abundantly expressed, mature miR-31 levels were selectively decreased in breast cancer cells, indicating a block at the post-transcriptional processing step. Treatment with the histone deacetylase inhibitor trichostatin A (TSA) restored miR-31 expression while concurrently suppressing Galectin-3, suggesting a potential regulatory link between the two molecules. RNA electrophoretic mobility shift assays (EMSA) demonstrated direct binding of recombinant Galectin-3 to in vitro-transcribed pre-miR-31. Protein-RNA docking analysis further supported this interaction, identifying the CUGGG motif (C35-G39) within pre-miR-31 as the key contact region interacting with the carbohydrate recognition domain (CRD) of Galectin-3. Functional analyses in MCF7 cells, which exhibit the highest endogenous Galectin-3 levels, showed that Galectin-3 knockdown markedly increased mature miR-31 expression without altering pri-miR-31 levels, confirming regulation at the processing stage. TaqMan™ microRNA profiling revealed that Galectin-3 depletion selectively altered a subset of miRNAs, including miR-31, suggesting partial remodeling of the cellular miRNA landscape. Collectively, our findings identify Galectin-3 as a negative regulator of miR-31 maturation in breast cancer cells and suggest a novel role for this lectin in post-transcriptional control of microRNA biogenesis.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663274","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":"Caenorhabditis elegans avoids epigallocatechin gallate (EGCG) through SRXA-7 G-protein coupled receptor.","authors":"YongJin Cheon, Hyeonjeong Hwang, Kyuhyung Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Flavonoids are plant-derived polyphenols that influence nematode behavior, yet their neuronal and molecular targets remain poorly understood. Here, we show that the free-living nematode Caenorhabditis elegans detects and avoids a green tea catechin epigallocatechin gallate (EGCG) via the SRXA-7 Gprotein coupled receptor (GPCR) in the ASH nociceptive neurons. EGCG and epicatechin gallate (ECG), both containing a galloyl group, trigger strong avoidance, unlike other green tea catechins lacking this moiety. EGCG avoidance behavior displays species- and strain-specific differences among Caenorhabditis species and wild C. elegans isolates. Moreover, it is dynamically modulated by prior experience and feeding state. The ASH chemosensory neurons are required for EGCG detection, with avoidance mediated through canonical GPCR signaling components including GRK-2, GPA-3, ODR-3, and TRPV channels OCR-2 and OSM-9. A targeted GPCR screen revealed that srxa-7 mutants exhibited specific defects in EGCG avoidance. EGCG-evoked calcium responses in ASH are reduced in srxa-7 mutants and restored by ASH-specific expression of srxa-7 cDNA. These findings indicate that SRXA-7 is a sensory receptor for galloylated polyphenols, uncovering the neuronal and molecular basis of adaptive aversive responses to dietary plant compounds in nematodes. [BMB Reports 2026; 59(8): 384-390].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"384-390"},"PeriodicalIF":4.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184582","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":"Generation, differentiation, and potential of three radial glial subtypes in human cortical organoids.","authors":"Mu Seog Choe, Jonghun Kim, In-Hyun Park","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Radial glia are the principal neural stem cells in the developing human cerebral cortex and have been classified as three molecularly distinct subtypes: ventricular radial glia (vRG), outer radial glia (oRG), and truncated radial glia (tRG). Human cortical organoids (hCOs) from human pluripotent stem cells that recapitulate the developmental program of the human cortex have shown this progenitor diversity. vRG and oRG are readily generated and identified in hCOs from most differentiation protocols with oRG emergence dependent on specific signaling pathways, such as LIF/STAT3 supplementation. However, tRGs that have only recently been defined at the molecular level have not been systematically examined in any organoid system. Here we review the biology, signaling, and lineage potential of each radial glial subtype and assess how faithfully they are represented in cortical organoids. We highlight and discuss the studies on the tRG from hCOs. We discuss data consistent with latent tRG competence in hCOs, including ependymal cell generation from radial glia within organoids, CRYAB-positive progenitors in three-dimensional culture systems, and tRG-associated transcriptomic shifts upon genetic perturbation, while noting that definitive tRG identification has not yet been achieved. However, definitive identification through combinatorial marker co-expression and morphological validation has not yet been achieved. Faithfully establishing molecular signatures and signaling frameworks for tRG and their existence in hCOs will provide the foundation for systemically investigating and function of this cell type in vitro, and we discuss future directions for resolving whether tRG are generated during the neurogenesis-to-gliogenesis transition. [BMB Reports 2026; 59(8): 373-383].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"373-383"},"PeriodicalIF":4.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410027","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":"Stem cell factor regulates endothelial HIF-2α expression during hypoxia-driven pathological angiogenesis.","authors":"Hayoung Jeong, Yang Hee Choi, Yubin Hwang, Minju Kim, June Hyeok Lee, Koung Li Kim, Wonhee Suh","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hypoxia-inducible factors (HIFs) act as master regulators of hypoxia-induced pathological angiogenesis, a hallmark of various ischemic ocular diseases. Recent evidence highlights the pivotal role of HIF-2α among HIF isoforms in endothelial cells (ECs) undergoing pathological angiogenesis under hypoxic conditions. However, the regulatory mechanisms underlying endothelial HIF-2α expression during hypoxia remain incompletely understood. Here, we demonstrated that stem cell factor (SCF) and its receptor, cKIT, upregulate HIF-2α expression in hypoxic ECs. Using the oxygen-induced retinopathy (OIR) mouse model, we observed that HIF-2α was highly expressed in cKIT-positive pathological neovessels in the retina, and SCF was upregulated mainly at astrocytes in the inner retinal layer. Experiments using cKIT mutant mice and anti-SCF neutralizing antibody demonstrated that inhibition of SCF/cKIT signaling significantly reduced retinal HIF-2α expression and pathological angiogenesis in mice with OIR. Moreover, HIF-2α inhibition abolished the SCF-induced increase in the angiogenic activity of human umbilical vein ECs (HUVECs) under hypoxic conditions. Mechanistic studies in HUVECs revealed that SCF enhanced HIF-2α protein levels without affecting HIF2A mRNA levels, through AKT- and ERK1/2-dependent phosphorylation of ribosomal protein S6 kinase β-1 under hypoxia. These findings provide novel insights into the regulatory mechanisms controlling HIF-2α expression in angiogenic ECs during hypoxia and suggest that the SCF/ cKIT/HIF-2α axis in hypoxic ECs represents a crucial pathway in the regulation of pathological angiogenesis in ischemic ocular diseases. [BMB Reports 2026; 59(8): 391-397].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"391-397"},"PeriodicalIF":4.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556303","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":"GRP78/BiP as a novel midbody component induces mitotic exit failure via PLK1 stabilization in hepatocellular carcinoma.","authors":"Sanghwa Kim, Yeonhwa Song, Su-Yeon Lee, Kang Mo Kim, Haeng Ran Seo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide and is associated with a poor prognosis, even when diagnosed in its early stages. Therefore, identifying novel HCC targets for therapeutic drug development is critically needed. Our proteomic analysis identified Glucose-regulated protein 78 (GRP78) as a potential new target, showing enrichment in HCC spheroids. We observed that post-surgery HCC patients with elevated GRP78 expression in non-tumor tissues had an unfavorable prognosis. Inhibition of GRP78 expression suppressed cell proliferation and reduced viability by controlling the DNA damage response in HCC cells. GRP78 expression peaked during the G2/M phase of mitosis and was predominantly localized to the cytoskeleton. However, its expression decreased as the cell cycle progressed from the G2/M to the G1 phase in HCCs. Overexpression of GRP78 in HCC cells increased the interaction between PLK1 and GRP78, leading to the stabilization of PLK1 in the midbody during cytokinesis. This stabilization resulted in the failure of cells to exit mitosis, producing multinucleated HCC cells. These findings reveal novel functional roles for GRP78 in disrupting mitotic activity through the stabilization of PLK1 at the midbody, thereby fostering polyploidy development in HCC. This suggests that inhibiting GRP78 is a promising approach for enhancing HCC therapy. [BMB Reports 2026; 59(8): 398-406].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"398-406"},"PeriodicalIF":4.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577076","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":"Urolithin A improves mitochondrial dysfunction induced by oxidative stress in human dermal papilla cells.","authors":"Iksun Kwon, Seo-Eun Lee, Yujin Kim, Shin-Hye Yu, Jeong Seon Yeo, Jeong-Wook Hwang, Chung Sub Han, Kyuboem Han, Chun-Hyung Kim, Young Cheol Kang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hair loss is a psychologically debilitating condition affecting social interactions. Despite extensive research, current interventions are transient and provide limited efficacy. Emerging evidence highlights that oxidative stress, resulting from mitochondrial dysfunction, impairs hair growth and disrupts hair cycle regulation. Urolithin A (UA), known to enhance mitochondrial function via mitophagy activation, has not yet been studied for its protective effects against hair loss. Here, we investigate whether UA protects against oxidative stress and promotes hair growth by restoring mitochondrial function in human dermal papilla cells (hDPCs) and clinical cases. hDPCs were subjected to H2O2 to induce oxidative stress and treated with various UA concentrations. Protective effects were assessed via mitochondrial function, morphology, apoptosis assays and Wnt/β-catenin signaling activity. Clinical evaluation involved measuring hair root volume and shedding rates following topical UA application. UA treatment improved mitochondrial function, reduced cell death under oxidative stress conditions, and activated Wnt/β-catenin signaling by increasing Wnt and β-catenin expression in hDPCs. Clinically, UA application led to increased hair root volume and decreased hair shedding. These dual effects on mitochondrial function and Wnt/β-catenin signaling highlight the potential of UA as a novel intervention for hair loss management.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306934","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":"Epigallocatechin gallate suppresses adipogenesis by targeting tetranectin and inhibiting its endocytosis via modulation of ERK and AKT signaling pathways.","authors":"Sana Iram, Jeongin Choi, Jihoe Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Epigallocatechin gallate (EGCG), a major polyphenol in green tea, exhibits anti-obesity effects, but its precise mechanism remains to be fully elucidated. In this study, we found that EGCG suppresses the adipocyte differentiation of 3T3-L1 cells, which was achieved with its treatment limited to the first two days post-differentiation induction. EGCG inhibited the tetranectin (TN)-mediated increase in ERK and AKT phosphorylation. EGCG efficiently removed TN in the differentiation medium, suggesting TN as a direct target. Furthermore, TN was found to undergo endocytosis during early differentiation, which was attenuated by EGCG, indicating a potential intracellular role for TN. Collectively, these findings demonstrate that EGCG suppresses adipogenesis by reducing TN availability in the medium and inhibiting its subsequent endocytosis, thereby modulating the ERK and AKT signaling pathways.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306974","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}