Functional & Integrative Genomics最新文献

{"title":"Integrative miRNA-multi-omics analysis of brain-metastasis predisposition in non-small cell lung cancer prioritizes HDAC inhibitors and anti-miR-330-3p as hypothesis-generating therapeutic candidates","authors":"Fahad Hassan Shah,&nbsp;Jung Sig Cho,&nbsp;Hiroyuki Konishi,&nbsp;Seung Hyeun Lee,&nbsp;Young Rae Jo,&nbsp;Seok Jae Huh,&nbsp;Junyang Jung,&nbsp;Na Young Jeong,&nbsp;Hyung-Joo Chung","doi":"10.1007/s10142-026-02099-1","DOIUrl":"10.1007/s10142-026-02099-1","url":null,"abstract":"<div><p>Brain metastasis (BM) is the leading cause of death in non-small cell lung cancer (NSCLC), yet its molecular drivers remain poorly targeted. Here we present an integrative in-silico pipeline that moves from miRNA discovery to therapeutic hypothesis generation. Reprocessing the GSE23019 miRNA microarray cohort (7 BM+ versus 5 BM- primary tumors) recovered the published BM-associated miRNAs miR-328 and miR-330-3p and, through validated miRNA-target interactions, yielded a signature of 828 up-regulated and 177 down-regulated genes enriched for extracellular-matrix and vasculature programs. Resampling analyses show this discovery-cohort signal is directionally reproducible but statistically fragile (no probe passes FDR control; permutation <i>P</i> = 0.29), so we carry it forward only as a seed for independent testing. In 519 TCGA lung adenocarcinomas, multi-omics factor analysis linked the signature to a latent stromal factor whose association with worse overall survival persisted after adjustment for stage, age, sex and smoking (adjusted HR 1.26 per SD, 95% CI 1.07–1.48), and miRNA-target anti-correlation nominated miR-330-3p-&gt; VEGFA as the strongest effector axis (Spearman rho = -0.37). Connectivity mapping against ~ 693,000 LINCS L1000 signatures identified histone deacetylase (HDAC) inhibition as the only enriched reversal mechanism (odds ratio 30.7, FDR = 0.0019). Blood-brain-barrier and lipophilicity machine-learning models ranked panobinostat first among 30 candidates, and anti-miR-330-3p is the prioritized miRNA therapeutic. Single-cell analysis of 208,506 lung-cancer transcriptomes and spatial co-localization across 13 NSCLC pucks mapped the program to cancer-associated fibroblasts, indicating the bulk signature tracks stromal composition. Knowledge-graph propagation recovered HDAC1 and HDAC2 among top-ranked genes, though sensitivity analyses show this convergence partly reflects hub structure. All nominations are hypothesis-generating and require experimental validation.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149332047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesizing multi-omics evidence of interface-specific selection in lung adenocarcinoma metastasis: A trait-origin-interface-function framework across lymph-node and brain ecosystems","authors":"Yiming Xu,&nbsp;Ruihao Zhang,&nbsp;Yiming Hu,&nbsp;Mingheng Yang,&nbsp;Hongyu Shan,&nbsp;Tingming Liang,&nbsp;Li Guo","doi":"10.1007/s10142-026-02094-6","DOIUrl":"10.1007/s10142-026-02094-6","url":null,"abstract":"<div><p>Lung adenocarcinoma (LUAD) mortality is driven largely by metastatic progression, yet lymph-node metastasis (LNM) and parenchymal brain metastasis (BrM) arise in fundamentally different immune and anatomical ecosystems. Here, we present an integrative review that conceptually synthesizes published genomic, single-cell, spatial-transcriptomic, proteomic and metabolomic findings. Our trait-origin-interface-function (TOIF) framework maps individual claims to trait origin, anatomical interface, metastatic stage and functional output, with separate annotations for evidence type and study context. In LNM, lymphatic access and nodal occupation are associated with remodeling of antigen presentation, progenitor T-cell maintenance, lymphoid organization, and immune-cell export; however, evidence for individual tumor-immune communication axes remains uneven. In BrM, neurovascular entry, perivascular survival, glial-myeloid signaling, metabolic adaptation, and restricted effector access represent separable bottlenecks. Cross-platform evidence indicates that shared genomic ancestry can coexist with site-enriched transcriptional, immune, and metabolic states, while temporal and lineage-resolved measurements help distinguish their possible pre-existence, selective expansion and acquisition after tissue exposure. We therefore propose a TOIF framework that links each candidate mechanism to the omics layers that support it, the spatial context in which it operates, and the experiment needed to test causality. This framework clarifies why similar low-cytotoxicity phenotypes may reflect distinct mechanisms in nodal and brain lesions, and provides a basis for multi-omics biomarker development and stage-matched therapeutic investigation in LUAD metastasis.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149332013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tritipyrum TtDHN3-TtLBD40 interaction conferred drought tolerance in wheat.","authors":"Mutong Li, Xiaolian Yang, Zhishun Yu, Yinjie Jiao, Jieting Yang, Suqin Zhang, Guangdong Geng","doi":"10.1007/s10142-026-02111-8","DOIUrl":"10.1007/s10142-026-02111-8","url":null,"abstract":"<p><p>Drought stress is a major threat that limits wheat productivity. In this study, the TtDHN3 gene was cloned from drought-tolerant Tritipyrum \"Y1805\" and transformed into common wheat \"1718\" using the coleoptile method. TtDHN3 expression levels in \"Y1805\" and the overexpression (OE) lines were upregulated under drought stress. After 24 h drought stress, TtDHN3 OE line showed significantly less leaf wilting compared with wild-type plants. At each experimental period, root length, shoot height, stem diameter, and fresh and dry weight of the roots and shoots in the OE lines were significantly higher than in wild-type plants. TtDHN3 OE significantly increased the activities of superoxide dismutase and catalase, enhanced the levels of soluble sugars, proline, chlorophylls, and carotenoids, and reduced malondialdehyde content and relative electrical conductivity under drought stress. In contrast, TtDHN3-silenced plants exhibited the opposite trends. Yeast two-hybrid assays suggested that TtDHN3 interacted with TtLBD40. This interaction was further confirmed by bimolecular fluorescence complementation and co-immunoprecipitation assays. Phenotypic and physiological-biochemical analyses demonstrated that TtLBD40 played a positive regulatory role in wheat drought responses. In summary, the interaction between TtDHN3 and TtLBD40 might enhance drought tolerance by improving osmotic regulation and reactive oxygen species scavenging. This study thus provides valuable genetic resources and a theoretical foundation for the molecular breeding of drought-tolerant wheat.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149332014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial mapping of neuroendocrine stress-response programs in head and neck squamous cell carcinoma reveals stromal niches associated with myeloid/Treg enrichment and a reproducible stress–B/plasma coupling","authors":"Anqun Tang,&nbsp;Wei Zhong,&nbsp;Yixin Tong,&nbsp;Zhi Liu,&nbsp;Yuxuan Zhu,&nbsp;Zimeng Zhou,&nbsp;Qingkun Jiang","doi":"10.1007/s10142-026-02101-w","DOIUrl":"10.1007/s10142-026-02101-w","url":null,"abstract":"<div><p>Chronic stress activates adrenergic and glucocorticoid signaling that shapes anti-tumor immunity in preclinical models, yet spatial evidence in human tumors is lacking. We mapped the spatial activity of neuroendocrine stress-response programs (β2-adrenergic, glucocorticoid receptor, neurotrophin, cAMP/CREB) in spatial transcriptomes of eight treatment-naïve head and neck squamous cell carcinomas (HNSCC; 11,224 Visium spots) and validated compartment associations in TCGA-HNSC (520 tumors). Program activity was spatially autocorrelated in all eight tumors (Moran’s I 0.038–0.156), peaked in fibroblast/endothelial stromal niches, and was spatially associated with myeloid/MDSC signatures rather than CD8 T-cell exclusion. In TCGA-HNSC, stress-response scores correlated with regulatory T cell, endothelial, exhaustion and stromal modules (ρ = 0.27–0.33; all BH <i>p</i> &lt; 0.001) but not survival, concentrated in HPV-negative tumors. Whole-transcriptome Open-ST (36,642 cells) confirmed stress-gene measurability and replicated the stress–B/plasma coupling, but the spot-level stromal pattern was not recapitulated within single cells. In a 3D Open-ST volume of a metastatic lymph node (1,054,579 cells), no coupling was conserved (stress–B/plasma partial <i>r</i> + 0.25 to − 0.01, <i>p</i> &lt; 0.001). Purpose-designed 7-plex multiplex immunofluorescence in 20 FFPE oral squamous cell carcinoma (OSCC; oral-cavity HNSCC) resections showed ADRB2-high stroma contained more CD68 + myeloid cells and FoxP3 + regulatory T cells (both <i>p</i> &lt; 0.001), with elevated myeloid PD-L1. In five matched primary–metastatic pairs, stromal ADRB2 and glucocorticoid receptor signaling was attenuated in metastatic lymph nodes (5/5 pairs; median metastatic-to-primary ratios 0.18 and 0.22) while PDGFRα/CCL19 + fibroblastic-reticular architecture was retained, consistent with a tumor-derived stromal mechanism hypothesis. The stress–immunity axis in HNSCC is thus best described as a stromal, myeloid/Treg-enriched niche association, providing a spatial framework for hypothesis-driven testing of adrenergic-pathway interventions.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De Novo transcriptome assembly and functional annotation in non-model organisms","authors":"Nihal Habib,&nbsp;Abderrazak Rfaki,&nbsp;Najib Al Idrissi,&nbsp;Chakib Nejjari,&nbsp;Lahcen Belyamani,&nbsp;Hassan Ghazal","doi":"10.1007/s10142-026-02090-w","DOIUrl":"10.1007/s10142-026-02090-w","url":null,"abstract":"<div><p>Advances in RNA sequencing have established transcriptomics as a key approach for investigating gene expression, regulation, and functional diversity across both model and non-model organisms. In the absence of high-quality reference genomes, de novo transcriptome assembly remains essential, yet its accuracy and reproducibility depend heavily on the choice and integration of computational strategies. This review provides a comprehensive and structured framework for de novo transcriptome reconstruction and functional annotation in non-model systems, integrating current best practices across quality control, assembly, redundancy reduction, and annotation workflows. We systematically compare short-read, long-read, and hybrid assembly approaches, and evaluate multi-layered annotation strategies combining homology-based, domain-based, and ontology-driven methods. We further highlight emerging developments, including long-read transcriptomics, machine learning-assisted annotation, orthology inference, and multi-omics integration, which improve transcriptome completeness and biological interpretability. Key limitations in current workflows are critically examined, including database biases, incomplete annotations, and challenges in isoform resolution, particularly in underrepresented taxa. By consolidating methodological advances with practical recommendations, this review proposes a reproducible and scalable roadmap for transcriptome analysis in non-model organisms. We also discuss future directions, including the development of inclusive reference databases, AI-driven annotation frameworks, and open, containerized infrastructures aligned with FAIR principles to support global transcriptomics research.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative bioinformatics and experimental validation of the prognostic and functional relevance of XDH and ITPA in non-small cell lung cancer","authors":"Weisong Zhang,&nbsp;Jianxiang Song,&nbsp;Hao Zhu,&nbsp;Yihao Wang,&nbsp;Hao Wang,&nbsp;Xia Li","doi":"10.1007/s10142-026-02100-x","DOIUrl":"10.1007/s10142-026-02100-x","url":null,"abstract":"<div><p>Purine metabolism has been implicated in tumor biology and immune regulation, but the clinical and biological relevance of purine metabolism-related genes in non-small cell lung cancer (NSCLC) remains incompletely defined. Transcriptomic data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project, together with TCGA clinical data, were analyzed to identify differentially expressed purine metabolism-related genes and assess their prognostic associations. Immune infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA), and single-cell transcriptomic datasets were analyzed to characterize the cellular context of candidate genes. Stemness features and drug sensitivity were assessed using transcriptome-based computational models. XDH and ITPA protein expression was examined by Western blotting and immunohistochemistry (IHC) in an independent NSCLC cohort and in cell models. Stable knockdown of XDH or ITPA was performed in H1299 cells, with key functional findings further evaluated in A549 cells. Cisplatin sensitivity was assessed using cell-viability dose-response assays in H1299 and A549 cells. Several purine metabolism-related genes were upregulated in NSCLC and associated with overall survival (OS). XDH and ITPA showed higher protein expression in tumor tissues and were associated with adverse clinicopathological features and poorer survival. Higher expression of these genes was also associated with altered immune infiltration patterns. The messenger RNA-based stemness index (mRNAsi) was associated with ITPA and XDH expression in different directions, whereas higher XDH expression was associated with higher predicted half-maximal inhibitory concentration (IC50) values for cisplatin. Knockdown of XDH or ITPA attenuated proliferative, clonogenic, migratory, and invasive phenotypes in H1299 cells, with key findings reproduced in A549 cells. XDH knockdown also reduced the experimentally determined cisplatin IC50 in both H1299 and A549 cells. XDH and ITPA may represent candidate prognostic and functionally relevant purine metabolism-related genes in NSCLC. The integrated clinical, computational, and cellular findings support their association with NSCLC progression-related phenotypes, while the underlying molecular mechanisms and broader clinical applicability require further investigation.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative multi-omics analysis reveals a GALNT6/Smad2/CDC7 axis promoting cisplatin resistance through enhanced DNA damage repair in bladder cancer","authors":"Yang Liu,&nbsp;Ziming Bian,&nbsp;Jianting Hu,&nbsp;Yuanxin Xie,&nbsp;Guanyu Cheng,&nbsp;Yan Zhang,&nbsp;Sairong Fan,&nbsp;Xiaoming Chen","doi":"10.1007/s10142-026-02103-8","DOIUrl":"10.1007/s10142-026-02103-8","url":null,"abstract":"<div><p>Cisplatin-based neoadjuvant chemotherapy remains an important treatment for advanced bladder cancer (BLCA), yet approximately half of patients derive limited benefit because of chemoresistance. Although DNA damage repair (DDR) is a key determinant of this resistance, how DDR heterogeneity contributes to chemoresistance remains unclear. Single-cell transcriptomic analysis revealed DDR heterogeneity among BLCA epithelial cells, with epithelial cells exhibiting higher DDR activity showing greater malignant potential. Bulk transcriptomic and proteomic analyses identified two molecular subtypes of BLCA. Compared with the DDR-Base subtype, the DDR-Active subtype exhibited enhanced DDR function and worse clinical outcomes. Integrative machine-learning modeling and SHapley Additive exPlanations (SHAP) prioritized <i>GALNT6</i> as a glycosylation-related regulator associated with the DDR-Active phenotype. <i>GALNT6</i> was highly expressed in the DDR-Active subtype and progressively increased along the epithelial-cell trajectory toward the DDR-enhanced malignant state. Functionally, <i>GALNT6</i> knockdown impaired DNA damage repair efficiency, thereby overcoming cisplatin resistance in BLCA. Mechanistically, GALNT6 stabilized SMAD2 through O-glycosylation, after which SMAD2 transcriptionally activated <i>CDC7</i> to enhance repair capacity against exogenous DNA damage. Moreover, <i>GALNT6</i> and <i>SMAD2</i> co-expression was a hallmark of the DDR-Active subtype and was associated with advanced tumor stage. This study defines clinically relevant DDR subtypes in BLCA and identifies the GALNT6/SMAD2/CDC7 axis as a driver of cisplatin resistance. These findings provide a biological framework for understanding heterogeneity in cisplatin response and for future treatment stratification.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host genomic context determines the direction of an oracle-predicted sequence effect: a composition-preserving CpG intervention in Enformer and Borzoi","authors":"Selahattin Alperen Uysal","doi":"10.1007/s10142-026-02097-3","DOIUrl":"10.1007/s10142-026-02097-3","url":null,"abstract":"<div><p>Sequence-to-function models are increasingly used as oracles to score designed regulatory elements, on the untested assumption that an effect measured at one locus holds at another. Taking chromatin and host loci from multiple sclerosis risk regions, we kept four questions apart: sequence realism, transfer of discrimination, edit stability, calibration. A sixth-order Markov chain reproduced the cell-type-specific motif enrichment a trained transformer missed, despite its lower held-out likelihood. Scores differ in level between loci far more than between inserts at one locus, yet inserts selected by an Enformer-derived index kept 85% of their advantage at four unseen loci. Once GC was matched, however, the index separated peak-derived from inaccessible sequence at none of 12 hosts, and from random sequence in opposite directions at different hosts. Placing identical inserts and an identical CpG edit at 24 host loci, the effect varied far beyond sampling noise on host identity alone (<span>(varvec{I}^{varvec{2}} varvec{= 95%})</span>), unpredicted by 18 host properties. It survives scoring only the bins the insert occupies (<span>(varvec{I}^{varvec{2}} varvec{= 92%})</span>, and across 200 loci), so is no artefact of aggregation; the apparent host dominance, however, falls from 25-fold to 3-fold under that localised score, and the one locus positive under the whole-window score reverses under it. Borzoi reproduced the heterogeneity but not its amplitude, and the objective did not predict lentiMPRA activity. For these two oracles and this edit, the size of a predicted effect depends on where it is measured, and its direction at any one locus is not robust.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histology-dependent coupling of TERT to the proliferation programme statistically accounts for much of the between-cohort heterogeneity in DNMT3B–TERT co-expression in oesophageal carcinoma: a 27-cohort meta-analysis and pan-cancer re-analysis","authors":"Mehdi Khorrami,&nbsp;Eshagh Parvaresh,&nbsp;Jahanbakhsh Asadi,&nbsp;Mohsen Tatar","doi":"10.1007/s10142-026-02106-5","DOIUrl":"10.1007/s10142-026-02106-5","url":null,"abstract":"<div><p>DNA methyltransferase 3B (DNMT3B) and telomerase reverse transcriptase (TERT) are induced in oesophageal carcinoma, and a reciprocal regulatory relationship has been proposed, but reported co-expression varies widely between studies. We assembled 26 public expression datasets into 27 cohort–histology strata comprising 1,787 treatment-naive primary tumours (673 oesophageal adenocarcinoma, EAC; 1,114 oesophageal squamous cell carcinoma, ESCC) under a pre-specified analysis plan. <i>DNMT3B</i> and <i>TERT</i> were positively correlated in both histologies (random-effects Spearman <i>r</i> = 0.29, 95% CI 0.14–0.42 in EAC; <i>r</i> = 0.15, 0.05–0.25 in ESCC), and the difference between them was not significant (<i>P</i> = 0.13). Between-cohort heterogeneity was substantial (<i>I</i>^<i>2</i> = 73% and 54%). What differed by histology, in post hoc analyses, was the coupling of <i>TERT</i> to proliferation: <i>r</i> = 0.29 (0.16–0.41) in EAC versus 0.05 (− 0.02 to 0.11) in ESCC (<i>P</i> = 5.2 × 10− 4). This coupling statistically accounted for 66% of the between-cohort variance in <i>DNMT3B</i>–<i>TERT</i> correlation (meta-regression slope 0.86, P = 1.3 × 10^− 6), a relationship not attributable to platform, <i>TERT</i> detectability or shared sampling error. A modest association survived adjustment for proliferation in both histologies and was also detectable in non-malignant mucosa (<i>r</i> = 0.30, P = 0.009), so it is not tumour-specific. Paired within-organ contrasts reproduced the adenocarcinoma–squamous difference (<i>P</i> = 7.4 × 10− 6). The positional methylation–expression gradient across the TERT locus in pooled oesophageal carcinoma (<i>ρ</i> = 0.42, P = 3.2 × 10− 5) disappeared within each histology and after histology adjustment (<i>ρ</i> = 0.01). Histology-aware analysis should precede mechanistic interpretation of epigenetic co-expression.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-4284 alleviates calcium oxalate monohydrate crystal-induced renal tubular epithelial injury in HK-2 cells via directly targeting MMP10","authors":"Zenglin Cui,&nbsp;Yijing Zhang,&nbsp;Zixiang Li,&nbsp;Kun Wang,&nbsp;Junqi Wang","doi":"10.1007/s10142-026-02065-x","DOIUrl":"10.1007/s10142-026-02065-x","url":null,"abstract":"<div><p>Calcium oxalate monohydrate (COM) nephrolithiasis has a high global incidence and postoperative recurrence. The study was to investigate miR-4284’s protective role and its targeting relationship with MMP10 in COM-induced HK-2 cell damage. HK-2 human renal tubular epithelial cells were exposed to COM crystals to establish an in vitro injury model. miR-4284 mimics and MMP10 overexpression plasmids were transfected for functional and rescue experiments. We adopted RT-qPCR, CCK-8, flow cytometry, LDH assay, ELISA, oxidative stress detection, western blot and dual-luciferase reporter assay to measure cell activity, apoptosis, inflammatory factors, antioxidant levels, tight junction proteins and target gene binding. COM treatment decreased miR-4284 expression and upregulated MMP10. miR-4284 improved cell viability, reduced apoptosis and LDH release. It suppressed inflammatory response and oxidative stress, and rescued Occludin, ZO-1 and E-Cadherin expression. Dual-luciferase assays confirmed direct binding between miR-4284 and MMP10 3’UTR. MMP10 overexpression abolished all protective phenotypes mediated by miR-4284. miR-4284 alleviates COM-triggered HK-2 cell injury by directly inhibiting MMP10. The miR‑4284/MMP10 axis identified in the HK‑2 in‑vitro cell model provides a preliminary mechanistic clue for understanding COM‑induced tubular injury, although its clinical relevance requires further validation in animal models and human specimens.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}