Frontiers in Molecular Biosciences最新文献

{"title":"Translational insights into miR-126 and miR-423: biomarkers and therapeutic targets in cancer, cardiovascular, metabolic and kidney diseases.","authors":"Małgorzata Rodzoń-Norwicz","doi":"10.3389/fmolb.2026.1813285","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1813285","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are key post-transcriptional regulators that orchestrate complex gene regulatory networks controlling endothelial function, metabolic adaptation, inflammation, and tissue remodeling. Among them, miR-126-3p, miR-126-5p, and miR-423-5p have emerged as context-dependent modulators linking vascular biology with cardiometabolic and oncologic disorders. MiR-126, through its 3p and 5p strands, plays a central role in maintaining endothelial integrity and angiogenic homeostasis. By modulating phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), mitogen-activated protein kinase (MAPK), and inflammatory signaling pathways, miR-126 regulates vascular repair, endothelial activation, and immune-vascular interactions. Reduced miR-126 expression is consistently associated with endothelial dysfunction, impaired angiogenic balance, and disease progression in diabetes, chronic kidney disease, and multiple cancers. In parallel, miR-423-5p regulates oxidative stress responses, transforming growth factor beta (TGF-β)-related pathways, and PI3K/AKT signaling in a context-dependent manner. Through modulation of redox balance, fibrotic remodeling, and cell survival pathways, miR-423-5p may exert either tumor-suppressive or pro-tumorigenic effects depending on cellular and microenvironmental conditions. In cardiometabolic and renal disorders, it contributes to microvascular dysfunction and inflammatory activation while also demonstrating translational potential as a circulating biomarker candidate. This review synthesizes shared and divergent signaling mechanisms governed by these miRNAs across disease states, emphasizing strand selection, target competition, and network-level cross-talk as determinants of context-specific outcomes. Understanding these multilayered regulatory interactions may support the development of network-oriented biomarker panels and precision RNA-based therapeutic strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1813285"},"PeriodicalIF":3.9,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836136","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":"Exome sequencing-based identification of <i>DNAAF1</i> variants implicated in male infertility and primary ciliary dyskinesia.","authors":"Baoqiong Liao, Wuming Xie, Mei Shuai, Lin Xiao, Jungao Huang, Ying He, Shuwen He","doi":"10.3389/fmolb.2026.1769803","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1769803","url":null,"abstract":"<p><p>Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive disorder caused by impaired cilia and flagella function. Despite advances in molecular diagnostics, pathogenic variants remain to be detected in a subset of clinically diagnosed individuals. In the present case, abdominal ultrasonography revealed situs inversus of the liver and spleen, and chest X-ray demonstrated dextrocardia. Semen analysis showed markedly reduced sperm motility, consistent with ciliary dysfunction, and the patient exhibited additional clinical features characteristic of PCD. Exome sequencing (ES) revealed biallelic variants in dynein axonemal assembly factor 1 (DNAAF1) (NM_178452.6), including a missense variant, c.524T>C (p.Leu175Pro), and a nonsense variant, c.1462C>T (p.Arg488*). Segregation analysis was performed in the available family members and confirmed that each parent carried one of the variants in a heterozygous state. Bioinformatic predictions supported the pathogenic potential of identified variants, suggesting that they likely underlie the ciliary defects observed in the affected individual. Taken together, these findings implicate previously reported <i>DNAAF1</i> variant c.1462C>T and newly identified variant c.524T>C in PCD associated with male infertility. The predicted structural perturbation in <i>DNAAF1</i> protein structure is likely to impair dynein arm assembly, leading to loss of ciliary motility and the resultant clinical phenotype.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1769803"},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836125","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":"Functional and genomic characterization of LCN2-deficient PC-3 cells reveals insights into prostate cancer progression.","authors":"Kiara Gäberlein, Diandra T Keller, Sarah K Schröder-Lange, Phillipp Torkler, Dominik G Grimm, Claus Steinlein, Thomas Haaf, Indrajit Nanda, Ralf Weiskirchen","doi":"10.3389/fmolb.2026.1730948","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1730948","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate Cancer-3 (PC-3) cells, commonly used as a model for aggressive, androgen-independent prostate cancer, display numerous genetic alterations that contribute to advanced disease, including the loss of tumor suppressors and dysregulated inflammatory signaling. Recent evidence has highlighted the pleiotropic roles of lipocalin 2 (LCN2) in promoting tumor cell proliferation, adhesion, and stress resistance. This study aimed to investigate the functional and molecular effects of <i>LCN2</i> depletion in PC-3 cells.</p><p><strong>Methods: </strong>We conducted a genetic analysis of both the parental PC-3 cell line and a newly created <i>LCN2</i>-deficient PC-3 clone #1 (PC-3 LCN2-KO#1), developed using CRISPR/Cas9 technology. Short tandem repeat (STR) analyses confirmed the authenticity and lineage of each cell line, while next-generation sequencing coupled with RT-qPCR validation was used to identify differentially expressed genes and any potential genomic changes resulting from the CRISPR/Cas9 editing process.</p><p><strong>Results and discussion: </strong>Our analysis aligned with our previous findings showing that <i>LCN2</i> is involved in inflammation, endoplasmic reticulum stress responses, and cytoskeletal organization. Previously we have shown that <i>LCN2</i>-deficient cells exhibited decreased invasiveness, disrupted F-actin dynamics, and increased sensitivity to stress-inducing conditions. Consistent with these observations, spectral karyotyping (SKY) and analysis of spontaneously occurring micronuclei revealed an elevated level of chromosomal aberrations in the <i>LCN2</i>-deficient cell line. These results emphasize the significance of <i>LCN2</i> in driving prostate cancer aggressiveness and provide a foundation for exploring targeted interventions that disrupt <i>LCN2</i>-mediated pathways in advanced disease.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1730948"},"PeriodicalIF":3.9,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836071","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":"Comparative proteomic analysis of colorectal cancer stem cells reveals potential biomarkers and altered pathways.","authors":"Ola J Hussein, Lubna Therachiyil, Shahd M Younis, Shaymaa Itani, Hanan H Abunada, Issam Tout, Cristina Maccalli, Hesham M Korashy","doi":"10.3389/fmolb.2026.1801265","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1801265","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) initiating/stem cells (CICs/CSCs) represent a rare tumor subpopulation with self-renewal capacity that drives tumor progression, recurrence, therapeutic resistance, and immune evasion. Despite extensive efforts to define CSCs using surface and functional markers, no universally accepted marker exists for CSC isolation and enrichment. Moreover, the molecular mechanisms underlying CSC-associated phenotypes remain incompletely characterized, highlighting the need for unbiased proteome-wide molecular profiling to better define CSC states and identify candidate biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>CSC-enriched spheroids were generated from two colorectal cancer cell lines (SW620 and HCT-116) using three-dimensional, serum-free culture conditions and compared with their corresponding parental adherent cells. Comparative proteomic profiling was performed using mass spectrometry-based label-free shotgun proteomics. Differentially abundant proteins were analyzed using Ingenuity Pathway Analysis (IPA) to identify overrepresented canonical pathways and predict upstream regulators. Selected differentially abundant proteins and predicted upstream regulators were validated by RT-qPCR and/or Western blotting.</p><p><strong>Results: </strong>Comparative proteomic profiling showed that CSC-enriched spheroids shared convergent pathway-level alterations despite cell line-specific differences in individual protein abundance. IPA pathway and functional analyses predicted activation of metabolic reprogramming, invasion, and hypoxia adaptation, along with predicted suppression of apoptotic pathways. Notably, HMGCS1, a key mevalonate-pathway enzyme, was strongly upregulated at both mRNA and protein levels in CSCs from both cell lines. MYC, MLXIPL, EGF/EGFR, VEGFA, and HIF-related signaling were among the top predicted upstream regulators shaping these alterations. In addition, altered expression of proteins involved in immunosuppressive signaling was observed in CSC-enriched spheroids, with TGF-β signaling emerging as a prominently activated upstream regulator, potentially contributing to CSC-associated epithelial-mesenchymal transition and immunomodulation.</p><p><strong>Conclusion: </strong>In summary, this study provides a better understanding of key dysregulated pathways and proteins in CRC CSCs, highlighting potential biomarkers and regulatory programs with relevance to stemness, immune modulation, and therapeutic resistance.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1801265"},"PeriodicalIF":3.9,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836063","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":"Oxidative stress mechanisms and potential biomarkers of methyl acetate poisoning: a urinary metabolomics study in rat model and human occupational cohort.","authors":"Jiayi Lv, Jiaming Guo, Shihua Wu, Yixian Ren, Shihao Tang, Xiumei Xing, Liping Zhou","doi":"10.3389/fmolb.2026.1801734","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1801734","url":null,"abstract":"<p><strong>Background: </strong>Methyl acetate (MA) is a common industrial solvent that causes rapid blindness in large exposures. Its toxicologic mechanism is not fully elucidated currently. The currently used clinical marker for MA poisoning, formic acid, is unable to differentiate between MA exposure and methanol exposure, which hinders accurate diagnosis and exposure source tracing, and impairs the development and implementation of front-end preventive and control measures.</p><p><strong>Objective: </strong>This study utilized a cross-species, untargeted metabolomics approach, combining data from animal models and human cohorts, aiming to identify potential biomarkers for MA poisoning and provide new insights into its toxicological mechanisms.</p><p><strong>Methods: </strong>Subacute poisoning rat models of MA and methanol were established via gavage administration (n = 6 per group) and urine samples were collected. Meanwhile, 8 occupationally exposed MA-intoxicated patients and 10 healthy controls were enrolled, with their urine samples also being collected. All samples underwent untargeted metabolomic analysis using UPLC-QTOF/MS for comparative profiling among MA-exposed rats versus control rats, MA-exposed rats versus methanol-exposed rats, and MA-exposed patients versus healthy controls.</p><p><strong>Results: </strong>A total of 41 and 16 significantly altered metabolites were identified in MA-exposed rat models and occupationally exposed human subjects, respectively. Pathway enrichment analysis further revealed key pathways including the tricarboxylic acid (TCA) cycle, purine metabolism, glutathione metabolism, cysteine and methionine metabolism, and one-carbon metabolism, suggesting conservation of MA-induced toxic responses across species. These results indicate that MA toxicity involves not only classical TCA cycle inhibition but also close association with systemic oxidative stress. 20-carboxy-leukotrieneB₄ (20-COOH-LTB₄) and S-adenosylhomocysteine (SAH) were significantly elevated in the MA exposure group in both rat and human samples, but were not detected in the methanol exposure group, showing high specificity and cross-species conservation.</p><p><strong>Conclusion: </strong>This study reveals MA toxicity mechanism via oxidative stress, aids in developing therapies and enhancing MA exposure risk management. And the study identifies 20 - COOH - LTB₄ and SAH as potential and sensitive biomarkers for MA intoxication, offering a tool for differentiating MA from methanol exposure clinically.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1801734"},"PeriodicalIF":3.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147813307","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":"Correction: A comprehensive review of diagnostic approaches for hepatitis D.","authors":"","doi":"10.3389/fmolb.2026.1842937","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1842937","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fmolb.2025.1598784.].</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1842937"},"PeriodicalIF":3.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147813304","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":"Editorial: Exploring miRNA roles in cancer pathogenesis and treatment, volume III.","authors":"Qinan Yin","doi":"10.3389/fmolb.2026.1833720","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1833720","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1833720"},"PeriodicalIF":3.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147813281","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":"Preksha Dhyana meditation modulates the serum metabolome in healthy and meditation-naïve participants.","authors":"Bassam Abomoelak, Nidhi Kapoor, Mary Schreck, Samani U Pragya, Samani C Pragya, Neelam Mehta, José Carlos Bozelli, Meera Shanmuganathan, Zachary Kroezen, Philip Britz-Mckibbin, Parvin Uddin, Pushya Veeramachaneni, Naina Mehta, Ray Prather, Arpit Mehta, Devendra Mehta","doi":"10.3389/fmolb.2026.1741802","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1741802","url":null,"abstract":"<p><p>The impact of various meditation interventions on modifying human health outcomes has been demonstrated at both cognitive and cellular levels. Preksha Dhyana (PD) meditation has previously shown effects on cognitive skills, transcriptome, and the DNA methylome in healthy, novice college students. In this study, we performed a cross-platform metabolomic and lipidomic analysis of serum samples collected from 38 healthy, meditation-naïve participants and five age-matched participants who served as controls. Serum samples were collected from both groups, at baseline (pre-meditation) and after an 8-week PD intervention. Analysis was conducted using capillary electrophoresis and reversed-phase liquid chromatography coupled to electrospray ionization-mass spectrometry, and higher serum concentration levels for four circulating metabolites, namely, hypoxanthine, oxoproline, choline, and cystine, were identified along with a series of lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) species (LPC 20:0, LPC 18:0, LPC 18:1, LPC 16:0, LPE 18:0, LPE 18:1, and LPE 22:6), following the PD intervention that satisfied a Bonferroni correction (p < 0.05, FDR). Pathway enrichment analysis revealed that these metabolites and lipids are primarily associated with the purine degradation cycle, glycerophospholipid metabolism, and glutathione metabolism, which are critical for maintaining cellular energy balance, preserving membrane integrity, and protecting against oxidative stress. A multi-omics analysis with Data Integration Analysis for Biomarker discovery using Latent approaches for Omics studies (DIABLO) revealed positive and negative correlations between these metabolites/lipids, DNA methylated sites (DMSs), and cognitive outcomes (r > 0.5). Overall, our findings suggest that the wellbeing experienced after PD meditation might be associated with bioactive metabolites and lipids, which may also function as epigenetic modifiers regulating gene expression and biological pathways.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov, Identifier NCT03779269.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1741802"},"PeriodicalIF":3.9,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147813249","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":"Editorial: Clinical molecular biological characteristics of malignant tumors.","authors":"Xi Yang","doi":"10.3389/fmolb.2026.1824594","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1824594","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1824594"},"PeriodicalIF":3.9,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767483","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":"Editorial: Unraveling enzyme-substrate dynamics in protein acylation and disease implications.","authors":"Shuyuan Cheng, Tong Liu, Jing Xing, Guoliang Zhang, Lin Zhang, Wei Zhao","doi":"10.3389/fmolb.2026.1842734","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1842734","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1842734"},"PeriodicalIF":3.9,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767457","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}