Frontiers in Cell and Developmental Biology最新文献

{"title":"Bisphenol A and prostate cancer: from population exposure to context-dependent mechanisms and translational implications.","authors":"Zhanhao Li, Hongliang Cao, Zihao Ye, Binbin Wang, Shuxin Li, Hao Wu, Zhiyuan Bai, Baoshan Gao","doi":"10.3389/fcell.2026.1949460","DOIUrl":"https://doi.org/10.3389/fcell.2026.1949460","url":null,"abstract":"<p><p>Bisphenol A (BPA) is a widespread endocrine-disrupting chemical with potential relevance to prostate cancer. This review provides a BPA-centered synthesis of evidence from human epidemiological studies, animal models, human prostate tissue and human-derived systems, and mechanistic investigations, while considering major BPA substitutes only where they inform substitution safety and class-informed assessment. Human studies provide limited and heterogeneous signals linking BPA exposure to prostate cancer incidence, prostate-specific antigen concentrations, and post-diagnosis outcomes, but causal inference is constrained by single-sample exposure assessment, cross-sectional or diagnosis-period designs, and heterogeneous endpoints. Experimental evidence supports a context-dependent model in which exposure timing, internal dose, hormonal milieu, androgen receptor status, cellular state, and subsequent biological challenge shape BPA-associated responses involving receptor signaling, epigenetic regulation, metabolism, redox homeostasis, and tissue organization. Rather than supporting uniform direct carcinogenicity, current evidence is more consistent with context-dependent modification of prostate biology, with distinct implications for cancer initiation, disease progression, hormone or treatment responsiveness, and biomarker alterations. These evidence domains should not be considered interchangeable. BPA measurements are not currently validated for prostate cancer screening, prognostic assessment, or treatment decisions. Progress will require repeated prospective biomonitoring, exposure-anchored human-relevant models, causal testing of proposed mediators, clinically verified outcomes, and targeted evaluation of major BPA substitutes such as bisphenol S (BPS) and bisphenol F (BPF), for which prostate-specific evidence remains comparatively limited.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1949460"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192501","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":"Betaine restores OPA1-mediated mitochondrial fusion in alveolar epithelial type 2 cells and ameliorates hyperoxic lung injury in newborn mice.","authors":"Jufeng Zhang, Hongyu Xie, Hui Xu, Meiling Zhang, You You, Jingwen Lv, Li Wang, Hongping Xia","doi":"10.3389/fcell.2026.1937629","DOIUrl":"https://doi.org/10.3389/fcell.2026.1937629","url":null,"abstract":"<p><strong>Introduction: </strong>Bronchopulmonary dysplasia (BPD) is a common chronic respiratory disease in preterm infants, characterized by impaired lung development. Mitochondrial dysfunction of alveolar type II epithelial (AT2) cells plays a critical role in the pathogenesis of BPD. Betaine is an endogenous methyl donor with anti-inflammatory and antioxidant properties. Our previous study demonstrated that plasma betaine levels were significantly decreased in preterm infants with BPD. The aim of this study was to investigate the effect of betaine on mitochondrial dysfunction of AT2 cells in BPD.</p><p><strong>Methods: </strong>Hyperoxia-induced BPD mouse models and hyperoxia-exposed MLE-12 cells were used. Proteomic analysis was performed on lung tissues from BPD and control mice. Mitochondrial structure and function were assessed by transmission electron microscopy, immunofluorescence, Western blotting, flow cytometry, and related assays. The OPA1 inhibitor MYLS22 was used to evaluate the role of OPA1 in the protective effect of betaine.</p><p><strong>Results: </strong>Hyperoxia exposure induced mitochondrial structural damage in AT2 cells and impaired lung development in BPD mice. Proteomic analysis revealed that differentially expressed proteins were significantly enriched in mitochondrial dysfunction pathways in the lungs of BPD mice. Family with sequence similarity 162 member A (FAM162A), a mitochondria-associated protein involved in mitochondrial homeostasis, was prominently downregulated. Betaine significantly increased the expression of FAM162A and optic atrophy 1 (OPA1), suppressed the activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) mediated integrated stress response, and alleviated cell apoptosis in AT2 cells in BPD mice. In vitro, betaine increased the expression of FAM162A and OPA1, improved mitochondrial dysfunction and decreased cell apoptosis, and the effect was abolished by the OPA1 inhibitor MYLS22 in MLE-12 cells exposed to hyperoxia.</p><p><strong>Discussion: </strong>Our findings revealed that betaine ameliorated OPA1-mediated mitochondrial fusion in AT2 cells and alleviated hyperoxic lung injury in newborn mice, providing new insight for the prevention and treatment of BPD.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1937629"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180435","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":"HDAC inhibitors in cancer therapy: sensitization mechanisms, combination strategies, and translational challenges.","authors":"Kun-Yao Liu, Xiang Zhao, Jia-Hui Liu, Mu-Nan Li, Hai-Ying Cui, Zhen Wang, Xin Zhou","doi":"10.3389/fcell.2026.1951750","DOIUrl":"https://doi.org/10.3389/fcell.2026.1951750","url":null,"abstract":"<p><p>Histone deacetylases (HDACs) are key regulators of chromatin architecture and gene expression, and their dysregulation is closely linked to tumorigenesis, making them attractive targets for cancer therapy. Histone deacetylase inhibitors (HDACis) exert broad antitumor effects by modulating both epigenetic and non-epigenetic pathways. Although HDACis have demonstrated clinical activity in selected hematologic malignancies, their limited efficacy as monotherapy and limited therapeutic benefit in many solid tumors continue to constrain their broader clinical utilization. Accumulating evidence suggests that HDACis may have greater clinical value as treatment sensitizers and synergistic partners in combination regimens. Across chemotherapy, radiotherapy, targeted therapy, endocrine therapy, and immunotherapy, they enhance therapeutic responses through a range of interconnected mechanisms, including chromatin relaxation, impairment of DNA damage repair, induction of apoptosis, suppression of cell cycle progression, inhibition of oncogenic signaling pathways, and remodeling of the immune microenvironment. In this review, we outline the classification and biological functions of HDACs, along with an overview of representative HDACis. We focus on the synergistic and sensitizing roles these agents play across major anticancer modalities and discuss the molecular mechanisms underlying their therapeutic effects. We further discuss key translational barriers, including insufficient isoform selectivity, off-target toxicity, tumor heterogeneity, and inefficient drug delivery. Finally, we highlight emerging strategies-including isoform-selective inhibitors, mechanism-based biomarkers, rationally designed combinations, targeted delivery platforms, and dual- or multi-target agents. Overall, this review provides a comprehensive overview of HDACi-based combination therapies and their therapeutic and translational implications.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1951750"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180490","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":"Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells.","authors":"Qinghui Shang, Xuepeng Bian, Shujie Lou","doi":"10.3389/fcell.2026.1929409","DOIUrl":"https://doi.org/10.3389/fcell.2026.1929409","url":null,"abstract":"<p><strong>Background: </strong>Beyond its traditional role as a glycolysis end-product, lactate is now recognized as an important signaling molecule influencing synaptic plasticity and mitochondrial activity.</p><p><strong>Objective: </strong>We examined whether lactate, acting through its receptor GPR81, improves synaptic plasticity-related protein expression by augmenting mitochondrial biogenesis and fusion.</p><p><strong>Methods: </strong>Primary hippocampal cells and Neuro-2A cells were studied. Hippocampal cells received L-lactate or the GPR81 agonist 3OBA. We measured ATP production and levels of proteins involved in mitochondrial biogenesis (PGC-1α, NRF1/2, TFAM), fusion (OPA1, MFN2), and synaptic plasticity (BDNF, PSD95, SYN). In Neuro-2A cells, pathways were blocked using the PGC-1α inhibitor SR-18292 or the fusion inhibitor MF18 after lactate/GPR81 activation.</p><p><strong>Results: </strong>L-lactate and 3OBA significantly enhance mitochondrial function, including increasing ATP production, upregulating key regulators of mitochondrial biogenesis (PGC-1α, NRF1/2, and TFAM), and promoting fusion proteins (OPA1 and MFN2) that maintain mitochondrial network integrity. These mitochondrial improvements were paralleled by elevated expression of synaptic plasticity-related protein expression (BDNF, PSD95, and SYN), suggesting functional coupling between metabolic and synaptic processes. Conversely, pharmacological inhibition of mitochondrial biogenesis (via PGC-1α inhibitor SR-18292) or fusion (using MF18) abolished lactate/GPR81-mediated benefits, resulting in reduced ATP levels, impaired mitochondrial membrane potential, and downregulation of synaptic proteins.</p><p><strong>Conclusion: </strong>Our findings reveal that lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells, highlighting a novel mechanism by which lactate supports neuronal energy demands and synaptic plasticity.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1929409"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180583","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":"Muscle satellite cell dysfunction in critical illness: niche biology, regenerative failure, and implications for recovery.","authors":"Takafumi Ono, Atsushi Asakura","doi":"10.3389/fcell.2026.1984134","DOIUrl":"https://doi.org/10.3389/fcell.2026.1984134","url":null,"abstract":"<p><p>Adult skeletal muscle can regenerate. After muscle injury, muscle stem cells (satellite cells) can generate new muscle fibers. Under normal conditions, satellite cells are mitotically quiescent and located beneath the basal lamina of muscle fibers. In response to regenerative stimuli, satellite cells activate and proliferate as myogenic precursor cells. After several rounds of cell division, these precursor cells differentiate and fuse to form new muscle fibers. A subset of proliferating myogenic precursor cells returns to a quiescent state to replenish the satellite cell pool through self-renewal. Intensive care unit-acquired weakness (ICU-AW) affects many critically ill patients partly due to acute muscle loss. It is a major physical component of post-intensive care syndrome. Current explanations of ICU-AW focus on rapid protein breakdown and impaired energy metabolism during the early catabolic phase, but these mechanisms do not fully explain why some survivors fail to rebuild muscle once the initial catabolic stress has subsided. In this review, we argue that persistent weakness may also reflect defective muscle regeneration, with satellite cell dysfunction and niche abnormalities as plausible contributors. Recent serial-biopsy studies suggest that dysfunction can occur without stem-cell depletion: satellite cell number can be preserved even when differentiation or later proliferative capacity is impaired in culture. We first review the normal satellite cell niche, including the parent fiber, microvasculature and perivascular cells, extracellular matrix, resident immune and interstitial cells, and systemic signals, with separate consideration of the diaphragm. We then examine how critical illness affects these compartments and how cell-intrinsic defects may additionally impair regeneration. We use this evidence to develop three working hypotheses (niche-detached activation, abortive myogenesis, and niche locking) and treat them as testable models rather than recognized mechanisms. Finally, we consider how future studies might measure, target, and test these processes.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1984134"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180530","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":"Integrated re-analysis of bulk and single-cell transcriptomic data reveals limited ferroptosis and neuroinflammation signatures after sevoflurane exposure in the aged rat hippocampus and human prefrontal cortex cells.","authors":"Zhenrong Zhang, Chen Hu, Yan Liu, Qin Zhang, Jiafei Liu, Zhihua Sun","doi":"10.3389/fcell.2026.1938601","DOIUrl":"https://doi.org/10.3389/fcell.2026.1938601","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Experimental studies have implicated ferroptosis in sevoflurane-associated neural injury, but the consistency of this signal across transcriptomic systems, species, and neural cell types remains uncertain. We therefore reassessed whether publicly available transcriptomic datasets support a coherent ferroptosis and neuroinflammation signature after sevoflurane exposure.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We re-analysed two public transcriptomic datasets: GSE141242, comprising hippocampal tissue from aged rats exposed to 2.5% sevoflurane for 4 h (n = 3) or oxygen control (n = 3), and GSE196239, comprising human embryonic prefrontal cortex mixed-cell cultures exposed to sevoflurane, propofol, recovery conditions, or untreated control (one library per condition). After quality control, 67,272 single cells were retained. Bulk differential expression was assessed with an empirical-Bayes linear model, whereas the unreplicated single-cell conditions were summarized descriptively using key-gene expression, predefined gene-set scores, and observed cell-type composition. In addition, qRT-PCR was performed in C6 glioma cells and HA astrocytes assigned to Control, 3.3% sevoflurane for 6 h, H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; (200 μM, 24 h), or Sevo + H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; groups to compare ferroptosis-related gene regulation across the four conditions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In the aged-rat hippocampus, no probe set reached FDR &lt; 0.05 (minimum FDR = 0.071), and the two groups did not separate clearly in principal-component space. In the human prefrontal cortex cultures, selected ferroptosis-related genes showed only small descriptive differences between the single control and sevoflurane libraries, and predefined gene-set summaries were likewise similar. Observed cell-type proportions differed by less than two percentage points, and no broad cell type showed a coherent sevoflurane-associated ferroptosis or inflammation pattern. The datasets were compared qualitatively rather than by formal cross-species correlation because of their marked biological and replication differences. In the four-group qRT-PCR experiment, sevoflurane and H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; each reduced GPX4 and SLC7A11 and increased ACSL4 and PTGS2 in C6 and HA cells; the combined group showed the largest changes, and all treatment groups differed from Control (Dunnett-adjusted P &lt; 0.05). Because the single-cell dataset contains only one library per condition, all between-condition single-cell comparisons are descriptive.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The available public transcriptomic data do not provide robust evidence for a coordinated ferroptosis or neuroinflammation program attributable to sevoflurane across the examined systems. The four-group experiment showed that sevoflurane and H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; each regulated ferroptosis-related genes, with the largest changes in the combined group, providing complementary evidence of pathway pertur","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1938601"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180544","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":"Editorial: Trogocytosis and cancer immunity: an intimate and unpredictable relationship.","authors":"Joyeeta Talukdar, Sorra Sandhya, Bikul Das, Suparno Chakrabarti, Subhradip Karmakar","doi":"10.3389/fcell.2026.1975241","DOIUrl":"https://doi.org/10.3389/fcell.2026.1975241","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1975241"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192507","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":"Artificial intelligence-based diagnostic model construction and quantitative analysis of retinal vein occlusion lesions using color fundus photographs.","authors":"Wenjuan Wu, Li Sun, Xingye Wang, Yan Liao, Jinrong Liu, Liwen He, Juan Liu, Jie Wang, Yilin Zhong, Hongyun Wu, Dennis S C Lam, Zhe Xu","doi":"10.3389/fcell.2026.1888364","DOIUrl":"https://doi.org/10.3389/fcell.2026.1888364","url":null,"abstract":"<p><p>Retinal vein occlusion (RVO) is the second most common retinal vascular disease worldwide, affecting over 7 million people in China. Currently, the clinical diagnosis and severity assessment of RVO largely rely on the subjective judgment of physicians, leading to high rates of missed diagnosis at an early stage, insufficient quantitative assessment, and poor consistency during follow-up. Most existing RVO-related AI models only support classification diagnosis and lack multi-dimensional quantitative assessment capabilities. This study evaluated an existing AI system (EVisionAI) for automatic segmentation and quantitative analysis of RVO lesions based on color fundus photographs, using a dataset of 106 RVO eyes and 60 normal control eyes. The system can simultaneously extract three core indicators: lesion characteristics, vascular morphology, and fundus tessellation density. The results showed that the Dice coefficients of the AI for the segmentation of hemorrhage, hard exudate, and cotton-wool spots were all above 0.78. After adjusting for demographic factors and systemic vascular risk factors in a multivariable GEE model, there were significant associations between the total area of hemorrhage, vascular fractal dimension, and vascular density for RVO (all P < 0.05), suggesting these metrics as promising objective biomarkers for RVO evaluation. A diagnostic model based on these multidimensional indicators achieved a cross-validated area under the curve (AUC) of 0.951 (SD: 0.018) for distinguishing RVO eyes from healthy controls. In summary, the proposed AI system enables precise, standardized, and reproducible multi-parametric quantitative evaluation of RVO. However, given the single-center cross-sectional design and the absence of external validation and disease controls, these findings are preliminary. Prospective multi-center studies with external validation are required to confirm its clinical utility.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1888364"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180454","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":"Stromal or exosome derived lncRNAs regulate stemness in hepatocellular carcinoma.","authors":"Tianyu Gao, Kai Li, Lin Wang, Xiaomeng Gui, Yuqing Xue, Haojing Li, Meng Qiao, Yaqin Tan, Hong Yang","doi":"10.3389/fcell.2026.1957154","DOIUrl":"https://doi.org/10.3389/fcell.2026.1957154","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains one of the most prevalent malignancies worldwide, with high recurrence rates and chemotherapy resistance posing major clinical challenges. Cancer stem cells (CSCs) are recognized as an important contributors of HCC initiation, metastasis, and recurrence. Within the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) can maintain CSC properties through intercellular communication. Exosomes serve as essential mediators of this process by delivering long noncoding RNAs (lncRNAs) from various TME cells (including CAFs, MSCs, macrophages, and HCC cells themselves) to recipient HCC cells.</p><p><strong>Methods: </strong>A literature search of PubMed and Web of Science Core Collection (inception to March 2026) was conducted using key terms including \"HCC\", \"CAFs\", \"MSCs\", \"Macrophages\", \"Exosome\", \"LncRNA\", and \"Neoplastic Stem Cells\". Studies were selected based on topic relevance and methodological rigor; those with incomplete or inaccessible data were excluded. The retrieved literature was synthesized to elucidate the mechanisms by which lncRNAs modulate downstream signaling pathways and to evaluate their translational potential as diagnostic biomarkers and therapeutic targets.</p><p><strong>Results: </strong>This review identifies multiple mechanisms through which stromal or exosome derived lncRNAs regulate HCC cell stemness, including YAP liquid-liquid phase separation, chromatin remodeling via recruitment of SWI/SNF, INO80, NuRD, and BRM/BRG1 complexes, Wnt/β-catenin pathway modulation through protein stabilization and competing endogenous RNA (ceRNA) networks, STAT3 pathway regulation via direct transcriptional repression and transcription factor recruitment, and BMP signaling pathway engagement. Functional classification reveals that these lncRNAs converge on core stemness pathways through complementary transcriptional, posttranscriptional, and protein-level regulatory mechanisms, while integrating signals from the TME.</p><p><strong>Conclusion: </strong>Stromal or exosome derived lncRNAs constitute a critical regulatory layer in HCC stemness maintenance and hold significant promise as noninvasive diagnostic biomarkers via liquid biopsy. Antisense oligonucleotide (ASO)-based therapeutic strategies targeting the stromal cell-lncRNA-CSC axis represent a promising direction. Nevertheless, systematic characterization of stromal or exosome derived lncRNA species, elucidation of lncRNA sorting and uptake mechanisms, and clinical validation of biomarker and therapeutic applications remain important challenges for future investigation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1957154"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180580","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":"ATG4B-dependent processing of tandem-domain BmLC3 exposes a Tyr136-regulated C-terminal fragment.","authors":"Won-Dong Shin, Hun-Joo Kim, Sang-Hee Ma, Sang-Won Park, Yong-Woo Jun, Do-Kyung Lee, In-Young Hwang, Deok-Jin Jang, Jin-A Lee","doi":"10.3389/fcell.2026.1957836","DOIUrl":"https://doi.org/10.3389/fcell.2026.1957836","url":null,"abstract":"<p><p>Autophagy-related protein 8 (ATG8) family proteins are ubiquitin-like modifiers that undergo ATG4-mediated processing before lipid conjugation. However, the structural and functional diversification of insect ATG8 proteins remains poorly understood. Here, comparative sequence analysis identified a 248-amino-acid LC3C-related protein from the silkworm <i>Bombyx mori</i> (BmLC3) containing two tandem LC3-like regions separated by an internal glycine at position 135 (G135), in addition to the canonical C-terminal glycine at position 248 (G248). In HeLa cells, N-terminally GFP-tagged BmLC3 generated a lower-molecular-weight product, whereas substitution of G135 with alanine prevented its formation. BmLC3 processing was markedly reduced in ATG4B-knockout cells and restored by expression of <i>B. mori</i> ATG4B (BmATG4B), demonstrating ATG4B-dependent cleavage at the internal junction. An isolated GFP-tagged C-terminal BmLC3 region showed increased punctate localization following starvation and bafilomycin A1 treatment, while BmATG4B also processed membrane-tethered mammalian ATG8 reporters in a cell-based cleavage assay. In a tandem fluorescent BmLC3 reporter, cleavage generated a C-terminal product beginning with Tyr136 that showed little mRFP signal, whereas Y136M increased both mRFP fluorescence and the mRFP/GFP band-intensity ratio. Together, these findings reveal a previously unrecognized mode of ATG8 diversification and support a model in which internal proteolysis couples fragment generation to N-terminal residue-dependent control of C-terminal product stability.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1957836"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180473","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}