Hereditas最新文献

{"title":"Novel KCNK3 variant in a child with pulmonary arterial hypertension.","authors":"Yi-Ming Zheng, Jia-Qi Jiang, Xuan Li, Hong-Biao Huang, Wen-Yu Zhuo, Xuan Tang, Ying Liu, Hai-Tao Lv","doi":"10.1186/s41065-026-00680-z","DOIUrl":"10.1186/s41065-026-00680-z","url":null,"abstract":"<p><p>BACKGROUND: Pathogenic variants in KCNK3 have been implicated in pulmonary arterial hypertension (PAH); however, the molecular mechanisms underlying this association remain insufficiently defined. METHODS: Whole-exome sequencing was performed in a child with PAH and her mother. The impact of the identified variant on protein stability was evaluated using cycloheximide chase assays. Apoptotic activity in transfected cells was assessed through flow cytometry and western blotting analysis. RNA sequencing was conducted to identify signaling pathways associated with altered gene expression. Oxidative stress levels were examined using inverted fluorescence microscopy. Expression levels of NFE2L2 was quantified by quantitative real-time polymerase chain reaction and western blotting. RESULTS: A novel heterozygous KCNK3 variant (c.607G > C, p.G203R) was identified. The substituted glycine residue demonstrated high evolutionarily conservation, and in silico analysis predicted structural alteration of the protein. The p.G203R variant was associated with reduced KCNK3 protein stability and an increase in apoptosis in vitro. Transcriptomic analysis indicated enhanced vascular smooth muscle cell migratory potential in cells expressing the variant. Increased cellular OS and apoptosis were observed in cells expressing p.G203R KCNK3. Bioinformatic analysis identified NFE2L2 as a key downstream effector. Expression of NFE2L2 was reduced in pulmonary artery endothelial cells expressing p.G203R KCNK3, while overexpression of NFE2L2 partially reversed variant-induced apoptosis. CONCLUSION: This study identifies a novel KCNK3 p.G203R variant associated with PAH and provides mechanistic evidence supporting its pathogenicity. These findings expand the variant landscape of KCNK3 in PAH and offer insights into disease pathogenesis that may inform future targeted therapeutic approaches. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716654","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":"Whole-transcriptome analysis of Aortic Stenosis reveals dysregulated RNA networks, immune cell infiltration, and NADK2 as a candidate regulator.","authors":"Feng-Xia Wang, Ming-Jun Duan, Hao-Qiang Guo, Jia-Qing Yu, Fen Liu, Nilupaer Aisikeer, Yi-Tong Ma, Xiang Xie","doi":"10.1186/s41065-026-00675-w","DOIUrl":"10.1186/s41065-026-00675-w","url":null,"abstract":"<p><p>BACKGROUND: Aortic stenosis (AS) is a common cardiovascular condition marked by progressive narrowing of the aortic valve and is associated with substantial morbidity and mortality. Although its clinical impact is well recognized, the molecular mechanisms driving AS progression remain incompletely defined, particularly with regard to the contributions of non-coding RNAs and immune–metabolic interactions. METHODS: High-throughput RNA sequencing combined with integrative bioinformatics analyses was performed on human aortic valve tissues from patients with AS to identify differentially expressed RNAs. Expression of Nicotinamide Adenine Dinucleotide Kinase 2 (NADK2) was validated using western blotting and quantitative polymerase chain reaction in both human AS specimens and murine AS models. Functional enrichment analyses, immune cell infiltration profiling, and weighted gene co-expression network analysis were applied to characterize regulatory networks and identify hub genes. RESULTS: A total of 1,443 messenger RNAs (mRNAs), 3,147 long non-coding RNAs (lncRNAs), and 145 circular RNAs (circRNAs) were differentially expressed in AS valve tissues, with the majority showing increased expression. Principal component analysis demonstrated clear separation between AS and control samples. Functional enrichment analyses linked differentially expressed mRNAs primarily to sensory perception and calcium signaling pathways, lncRNAs to embryonic development–related processes, and circRNAs to protein regulatory functions. NADK2 was identified as a hub gene and was significantly upregulated at both the mRNA and protein levels in valve tissues from patients with AS and in the murine AS model. Immune infiltration analysis indicated increased proportions of CD4⁺ memory T cells and CD8⁺ T cells in AS, with strong positive correlations observed between these immune cell populations and NADK2 expression. Weighted gene co-expression network analysis further supported NADK2 as a key candidate regulator within the disease-associated magenta module. CONCLUSION: This study delineates comprehensive RNA regulatory networks in patients with AS and identifies NADK2 as a key molecular contributor to disease pathogenesis. Its consistent upregulation across species, together with close associations with immune dysregulation and co-expression network modules, supports its potential relevance as a therapeutic target in AS. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716660","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":"Cellular plasticity and heterogeneity underlying therapy resistance in 3D cervical cancer models.","authors":"Mercedes Olvera-Valencia, Adriana Grijalva-Pérez, Oliver Millan-Catalan, Martha Estela Albino-Sánchez, Manuel Humberto Cháirez-Ramírez, Rocío Méndez-Martínez, Eduardo López-Urrutia, Carlos Pérez-Plasencia, Alejandro García-Carrancá","doi":"10.1186/s41065-026-00668-9","DOIUrl":"10.1186/s41065-026-00668-9","url":null,"abstract":"<p><p>Despite the success of prophylactic vaccination and screening programs, cervical cancer remains a major cause of cancer-related morbidity and mortality worldwide, particularly in low- and middle-income countries. In cervical cancer, therapeutic resistance cannot be explained by viral status alone and instead reflects broader tissue level and microenvironmental determinants. Increasing clinical and experimental evidence indicates that these processes are driven by dynamic cellular plasticity and microenvironmental adaptation rather than fixed genetic alterations alone. Three-dimensional (3D) model systems, including multicellular spheroids and patient-derived organoids, have transformed the study of cervical cancer by preserving tissue architecture, epithelial hierarchy, and spatial gradients of oxygen, nutrients, and signaling cues that are lost in conventional two-dimensional cultures. These models reveal how hypoxia, metabolic reprogramming, extracellular matrix interactions, and immune modulation converge to promote reversible, stress-tolerant cell states with stem-like features. In particular, 3D systems uncover hypoxia-associated redox adaptation, enhanced DNA damage repair capacity, and sustained viral oncogene expression within spatially defined niches that exhibit reduced sensitivity to cisplatin and radiotherapy. Here, we synthesize current advances in 3D cervical cancer modeling to illustrate how these platforms enable direct observation of resistance mechanisms that remain inaccessible in 2D systems. We discuss how organoids and advanced 3D culture systems provide mechanistic insight into plasticity programs operating in HPV-associated cervical cancer, tumor microenvironment remodeling, and the emergence of therapy-resistant states, while offering improved translational relevance for drug testing. Collectively, this review positions 3D cell culture models as a key tool for dissecting the dynamic biology of cervical cancer resistance and for guiding the rational design of therapeutic strategies aimed at preventing relapse.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13188776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689919","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":"VEZF1 inhibits ovarian cancer cell ferroptosis and acts as an oncogene via the miR-545-3p/PLAG1 axis.","authors":"Wei Shi, Weiwei Feng, Jing Wan, Xiao-Ping Wan","doi":"10.1186/s41065-026-00672-z","DOIUrl":"10.1186/s41065-026-00672-z","url":null,"abstract":"<p><p>BACKGROUND: Ovarian cancer (OC) is a fatal carcinoma for women. This study attempts to explore the role of vascular endothelial zinc finger 1 (VEZF1) in OC cell ferroptosis, thereby finding a new target for OC treatment. METHODS: Expressions of VEZF1, miR-545-3p and PLAG1 in HOSE cell line and OC cell lines were determined by RT-qPCR and western blot analysis. After VEZF1 was silenced in cells, cell proliferation was examined, contents of ROS, MDA, Fe2+, GSH were detected, and expressions of ACSL4 and GPX4 were tested. Afterwards, the binding relation between VEZF1 and miR-545-3p and between miR-545-3p and PLAG1 were verified. Functional rescue assays were formulated to validate the role of miR-545-3p knockdown or PLAG1 overexpression in OC cell ferroptosis. RESULTS: VEZF1 was overexpressed in OC, and VEZF1 silencing reduced cell proliferation, elevated levels of ROS, MDA, Fe2+, inactivated levels of GSH and GPX4, and enhanced ACSL4 expression. Functionally, VEZF1 transcriptionally inhibited miR-545-3p, and miR-545-3p targeted and inhibited PLAG1. miR-545-3p knockdown or PLAG1 overexpression could reverse the effect of VEZF1 silencing on OC cell ferroptosis. CONCLUSION: VEZF1 was overexpressed in OC and it limited OC cell ferroptosis by transcriptionally inhibiting miR-545-3p and elevating PLAG1 expression. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13188589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147672612","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":"Protective effect of Saikosaponin D modulating endoplasmic reticulum stress mediated by TLR4/MyD88/NF-κB/NLRP3 pathway on cholestatic liver injury.","authors":"XianMeng Meng, Wei Chen","doi":"10.1186/s41065-026-00669-8","DOIUrl":"10.1186/s41065-026-00669-8","url":null,"abstract":"<p><strong>Objective: </strong>Cholestatic liver injury (CLI) has lacked a potent treatment due to its incompletely understood pathogenesis. Saikosaponin D (SSD), the main active ingredient of the traditional Chinese medicine Bupleuri Radix, has significant anti-inflammatory and hepatoprotective effects and inhibits hepatic fibrosis. This study specifically investigated the protective effects of SSD in CLI and its related mechanisms.</p><p><strong>Methods: </strong>In bile duct ligation (BDL)-induced CLI in mice, the protective effect of SSD was assessed by serum biochemical index analysis, HE staining of liver tissue, Sirius red staining, immunohistochemistry and ELISA. Bile acid-induced human HepG2 cell line was taken to study the protective effect and potential mechanism of SSD against CLI in vitro. TLR4/MyD88/NF-κB/NLRP3 pathway-related proteins in mouse liver tissues or HepG2 cells were detected by Western blot or immunofluorescence.</p><p><strong>Results: </strong>SSD dose‑dependently improved liver function and reduced hepatocyte necrosis, collagen deposition, and apoptosis. It attenuated oxidative stress injury, inflammatory responses, and endoplasmic reticulum stress (ERS) in BDL mice. SSD also mitigated bile acid‑induced injury and ERS in HepG2 cells. Moreover, SSD suppressed the activation of the TLR4/MyD88/NF‑κB/NLRP3 pathway. The TLR4 inhibitor TAK‑242, similar to SSD, ameliorated bile acid‑induced HepG2 cell injury and ERS, whereas the TLR4 agonist LPS counteracted the protective effects of SSD and its inhibition of ERS in bile acid‑stimulated HepG2 cells.</p><p><strong>Conclusion: </strong>SSD attenuates CLI, an effect that may be associated with the suppression of the TLR4/MyD88/NF‑κB/NLRP3 pathway and the subsequent inhibition of ERS.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662364","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":"Curcumin inhibits chondrocyte apoptosis and inflammation in osteoarthritis via the miR-338-3p/EIF4A1 signaling axis.","authors":"Na Dai, Bin Shi","doi":"10.1186/s41065-026-00674-x","DOIUrl":"10.1186/s41065-026-00674-x","url":null,"abstract":"<p><p>OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disorder mainly characterized by articular cartilage degradation. Curcumin, the primary bioactive compound derived from turmeric, exhibits anti-inflammatory, antioxidant, and anti-catabolic activities. This study aimed to explore the therapeutic potential of curcumin in OA and its underlying mechanism involving the microRNA-338-3p (miR-338-3p)/Eukaryotic Translation Initiation Factor 4A1 (EIF4A1) signaling pathway. METHODS: Mouse models of OA were established, including groups treated with curcumin or intra-articular injection of miR-338-3p agomir, along with an in vitro chondrocyte model. Modulation of miR-338-3p and EIF4A1 expression was achieved through siRNA interference. Gene expression was quantified via quantitative real-time polymerase chain reaction and Western blot; the targeting interaction between miR-338-3p and EIF4A1 was confirmed using a luciferase reporter assay; and cellular viability and inflammatory mediator levels were evaluated with Cell Counting Kit-8, flow cytometry, and enzyme-linked immunosorbent assay. Cartilage tissue pathology was also examined. RESULTS: EIF4A1 was markedly upregulated in OA cartilage, whereas miR-338-3p targeted and suppressed EIF4A1 expression. Curcumin administration elevated miR-338-3p levels and reduced EIF4A1 expression. Moreover, curcumin, miR-338-3p overexpression, and EIF4A1 knockdown attenuated chondrocyte apoptosis, enhanced proliferation, and modulated apoptosis-related protein expression (decreasing cleaved caspase-3 and Bax, increasing Bcl-2). Curcumin also suppressed the secretion of inflammatory cytokines (IL-6, TNF-α, IL-1β, etc.), decreased synthesis of matrix-degrading enzymes (Matrix Metalloproteinase-13 (MMP13), A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS)), and reduced OARSI scores, ultimately ameliorating OA progression. CONCLUSION: These results demonstrate that curcumin mitigates chondrocyte apoptosis, attenuates cartilage inflammation, and downregulates joint matrix-degrading enzyme expression in OA through the miR-338-3p/EIF4A1 axis, suggesting this pathway as a promising target for gene therapy in OA. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645071","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":"Cancer-associated fibroblasts and immune escape-related genes serve as biological markers for the prognosis of colorectal cancer.","authors":"Xia Liu, Aorong Shi, Bai Dai, Yue Chang, Fen Yun, Huan Guan, Rina Sha, Yongfeng Jia","doi":"10.1186/s41065-026-00676-9","DOIUrl":"10.1186/s41065-026-00676-9","url":null,"abstract":"<p><p>BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor with a steadily rising incidence rate, and it is often diagnosed at an advanced stage. Immunotherapy has emerged as a promising alternative to surgical resection. Cancer-associated fibroblasts (CAFs) play a critical role in the tumor microenvironment (TME) and are closely associated with tumor immune evasion. This study aims to identify genes associated with CAFs and immune evasion in CRC, and to explore their underlying mechanisms and potential clinical applications in CRC. METHODS: Based on CRC transcriptomic data from TCGA and GEO (GSE39582), this study identified differentially expressed genes associated with tumor-associated fibroblasts and immune evasion (CAFIERDEGs) and performed GO/KEGG functional enrichment analysis on them. A prognostic risk model was constructed based on CAFIERDEGs, followed by survival analysis and validation. Additionally, key genes were identified through the construction of a protein-protein interaction (PPI) network, and differences in immune checkpoint expression, immune cell infiltration, and immunotherapy response were systematically evaluated across different risk groups. Finally, the key genes were experimentally validated using single-cell RNA sequencing, immunohistochemistry, and qPCR. RESULTS: Five hub genes (SOX2, CXCL11, SPP1, APOE, and CXCL8) were screened. These genes are involved in the regulation of the immune response, cytokine activity, and the Toll-like receptor signaling pathway. CRC patients were classified into two distinct molecular subtypes based on the expression profiles of these genes. The prognostic risk model revealed significant differences in overall survival rates. The tumor immune dysfunction and rejection (TIDE) score was significantly lower in the low-risk group. The tumor mutational burden (TMB) was higher, and the expression of most immune checkpoint genes increased. This indicates a stronger potential reactivity to immunotherapy. Experiments confirmed that the expressions of CXCL8, CXCL11, and SPP1 were significantly upregulated in CAFs, while APOE and SOX2 expressions were significantly downregulated. CONCLUSION: This study identified five CAFIERGs and constructed a prognostic model for CRC by integrating CAFs and immune escape-related genes. This model can predict the immunotherapy response and prognosis of CRC patients. These findings offer potential therapeutic targets for improving prognostic evaluation and guiding immunotherapy strategies in CRC patients. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633389","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":"Serum LINC01127 serves as a diagnostic biomarker for sepsis and its predictive value for clinical outcomes.","authors":"Congcong Li, Xiao Gui, Haiyuan Zhu, Jinhui Wang, Yu Xie, Lilin Wang, Yongyang Tian, Shun Li","doi":"10.1186/s41065-026-00670-1","DOIUrl":"10.1186/s41065-026-00670-1","url":null,"abstract":"<p><p>BACKGROUND: This study aims to investigate the role of LINC01127 in sepsis and evaluate its potential clinical value. METHODS: This study included 102 sepsis patients and 102 controls matched for age and gender. Serum levels of LINC01127 and miR-34b-5p were measured using quantitative real-time PCR (RT-qPCR). Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic efficacy of LINC01127 for sepsis, while Kaplan-Meier curves evaluated its prognostic significance during 28-day follow-up. Lipopolysaccharide (LPS)-induced THP-1 cells were used to simulate an in vitro sepsis model. Enzyme-linked immunosorbent assay (ELISA) measured proinflammatory factor levels, and flow cytometry assessed apoptosis. RESULTS: Serum LINC01127 exhibited downregulation in sepsis-affected individuals, while miR-34b-5p was upregulated. ROC curve analysis demonstrated that LINC01127 possesses good diagnostic value for sepsis. Kaplan-Meier analysis showed that low LINC01127 levels were associated with poorer prognosis during the 28-day follow-up. Bioinformatics analysis successfully predicted a binding site for miR-34b-5p on LINC01127, and dual-luciferase reporter (DLR) and RNA immunoprecipitation (RIP) assays confirmed their target relationship. Cell experiments demonstrated that upregulating LINC01127 significantly reduced the apoptosis and inflammation triggered by LPS, while increasing miR-34b-5p expression markedly reversed these effects. CONCLUSION: LINC01127 may serve as a promising biomarker for sepsis, alleviating apoptosis and inflammatory responses through targeting miR-34b-5p. This offers novel insights into sepsis diagnosis and treatment. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627681","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":"Extracellular matrix-growth factor signalling drives the oncogenic mir-125b-2/UCK2 axis in hepatocellular carcinoma.","authors":"YunFeng Zhao, HaoXin Shen, Yibo Sun, JinKun Song, Chen GuangSun, JinXiu Li, HongYu Wang, YinSen Song","doi":"10.1186/s41065-026-00673-y","DOIUrl":"10.1186/s41065-026-00673-y","url":null,"abstract":"<p><p>BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by coordinated transcriptional and post-transcriptional dysregulation. We sought to identify clinically relevant miRNA–mRNA regulatory axes with cross-cohort, multi-layer validation. METHODS: Tumor–normal differential expression was integrated across TCGA-LIHC and independent microarray cohorts. Predicted miRNA targets were filtered by inverse-direction overlap with consensus DEGs and evaluated for activity–abundance coherence and survival relevance. An eight-feature axis (four miRNAs and four target-set activities) was modeled using penalized Cox regression with cross-validation and externally validated. RESULTS: Four recurrent miRNAs were identified (miR-125b-2 downregulated; miR-21, miR-221, miR-9-1 upregulated). miR-125b-2 showed the strongest inverse coherence with its target set (ρ = −0.41, P < 1 × 10⁻¹²). The composite axis stratified TCGA overall survival (log-rank P < 0.0001) and validated in GSE31384 (HR = 1.62, 95% CI 1.15–2.28; C-index = 0.66). Seven targets met FDR ≤ 1%, with UCK2 exhibiting the strongest adverse association (HR = 2.78, P = 2.7 × 10⁻⁹). UCK2 was overexpressed, hypomethylated, enriched in epithelial compartments, and linked to proliferative and ECM/growth-factor signaling programs. Functional assays demonstrated that UCK2 knockdown suppressed proliferation, clonogenicity, and migration, whereas overexpression enhanced these phenotypes. CONCLUSIONS: The miR-125b-2/UCK2 axis defines a metabolically driven, epithelial proliferative program coupled to ECM/GF signaling and represents a validated prognostic and biologically actionable node in HCC. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608631","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":"Recognition and confirmation of key genes associated with nicotinamide metabolism in acute myocardial infarction.","authors":"Nan Qu, Fawen Bai, Jin Lan","doi":"10.1186/s41065-026-00671-0","DOIUrl":"10.1186/s41065-026-00671-0","url":null,"abstract":"<p><p>BACKGROUND: The role of nicotinamide in improving cardiac function suggests its therapeutic benefit for acute myocardial infarction (AMI). This study aims to identify key genes associated with nicotinamide metabolism in AMI, offering novel insights into its therapeutic management. METHODS: The GSE60993 and GSE61144 datasets were retrieved from the database. Mendelian randomization (MR) analysis, Cytoscape-plugin cytoHubba algorithms, and expression validation were used to identify key genes linked to nicotinamide metabolism. Subcellular localization, gene set enrichment analysis (GSEA), immune infiltration analysis, drug prediction, and molecular docking were then performed. Finally, the expression of key genes was validated experimentally in clinical samples. RESULTS: Three key genes (FLT3LG, ITGB7, and PARP1) were found to be causally associated with AMI, ranking in the top three of the three Cytoscape-plugin cytoHubba algorithms. FLT3LG and ITGB7 were identified as risk factors (odds ratio [OR] > 1, P-value < 0.05), while PARP1 was a protective factor (OR < 1, P-value < 0.05). Expression analysis in GSE60993 and GSE61144 confirmed similar trends for these genes. FLT3LG and ITGB7 were predominantly located in the cytoplasm, whereas PARP1 was mainly in the nucleus. GSEA results indicated involvement of these genes in pathways such as the ribosome, oxidative phosphorylation, and spliceosome. Immune infiltration analysis showed that neutrophil scores were higher in AMI and negatively correlated with ITGB7 (cor = -0.84), PARP1 (cor = -0.75), and FLT3LG (cor = -0.86). Drug prediction and molecular docking revealed strong correlations between the key genes and Tetradioxin, with excellent binding ability. Expression trends of the three genes in clinical samples aligned with bioinformatics findings. CONCLUSIONS: This study identified three genes associated with nicotinamide metabolism whose altered expression or function may have played a role in the pathological process of AMI. These genes could provide potential reference points for the diagnosis and treatment of AMI. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147573961","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}