Hereditas最新文献

{"title":"Comprehensive molecular analyses of a circadian rhythm-related gene diagnostic model and immune infiltration using machine learning methods in sepsis-associated acute kidney injury.","authors":"Yuzhen Luo, Tangjuan Liu, Yiqiang Chen","doi":"10.1186/s41065-026-00698-3","DOIUrl":"10.1186/s41065-026-00698-3","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to explore hub circadian rhythm-related genes (CRRGs) associated with sepsis-associated acute kidney injury (saAKI) using machine learning algorithms to provide novel ideas for the diagnosis and treatment of this disease.</p><p><strong>Materials: </strong>Two AKI datasets (GSE30718 and GSE139061) were obtained from the Gene Expression Omnibus (GEO) database. We initially identified differentially expressed genes (DEGs) and performed WGCNA to identify candidate CRRGs. Following this, diagnostic CRRGs were identified on the basis of machine learning algorithms. The ssGSEA method was used to measure the link between hub CRRGs and immune cells. GSEA and GSVA were used to understand the relevant functions and pathways. The hub CRRGs were validated using the GSE255281 dataset and RT‒qPCR of clinical blood samples.</p><p><strong>Results: </strong>On the basis of the DEGs and WGCNA results, a total of 21 candidate CRRGs were obtained for saAKI. Seven diagnostic CRRGs were identified via the Lasso, random forest (RF) and SVM-RFE algorithms. We then constructed a predictive nomogram using the diagnostic CRRGs, and the calibration, decision and ROC curves revealed that it had high diagnostic efficiency. Through the evaluation of 2 subdatasets, 4 hub CRRGs (DEFB1, EGF, REN and PTPRD) were ultimately identified. Immune cell infiltration analysis indicated that there might be immune dysregulation in saAKI. GSEA and GSVA revealed different biological functions and pathways related to immunity, inflammation, metabolism and material transport that might exist in different subgroups of hub CRRGs. The validation dataset GSE255281 and RT‒qPCR analysis verified the expression of EGF and PTPRD.</p><p><strong>Conclusion: </strong>Our research utilized comprehensive machine learning methods to construct a CRRG-based diagnostic model for saAKI. The identified CRRGs may be potential biomarkers of saAKI, and this study may provide new strategies for the diagnosis and treatment of saAKI.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224540","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":"MIR9-3HG/let-7c-5p/THBS1 axis promotes hepatocellular carcinoma progression.","authors":"Jinmin Su, Jiaoling Gu, Zhizhong Lu","doi":"10.1186/s41065-026-00694-7","DOIUrl":"10.1186/s41065-026-00694-7","url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNAs (lncRNA) are key regulators in hepatocellular carcinoma (HCC). However, the role of MIR9-3HG in HCC remained unclear.</p><p><strong>Objective: </strong>This study investigated the expression, clinical significance, and molecular mechanism of MIR9-3HG in HCC.</p><p><strong>Methods: </strong>MIR9-3HG, hsa-let-7c-5p, and THBS1 levels were quantified via RT-qPCR in 179 paired HCC tissues and cell lines. Associations between MIR9-3HG expression and clinicopathological features were analyzed using χ² test. The prognostic value was assessed using Kaplan-Meier and Cox regression analyses. The biological functions of MIR9-3HG were evaluated through CCK-8, Transwell assays. The competing endogenous RNA (ceRNA) targeting relationship was validated using dual-luciferase reporter.</p><p><strong>Results: </strong>MIR9-3HG was significantly upregulated in HCC tissues and cell lines. High MIR9-3HG expression correlated with advanced TNM stage, higher Edmondson-Steiner grade, vascular invasion, and poor overall survival, and was identified as an independent prognostic factor. Hsa-let-7c-5p expression was negatively correlated with MIR9-3HG and THBS1in HCC tissues. In vitro experiments, silencing MIR9-3HG inhibited HCC cell proliferation, migration, and invasion. Luciferase reporter assays demonstrated that MIR9-3HG functioned as a ceRNA to sponge hsa-let-7c-5p. In turn, hsa-let-7c-5p directly targeted and negatively regulated THBS1.</p><p><strong>Conclusion: </strong>MIR9-3HG promoted HCC aggressiveness by acting as a ceRNA for hsa-let-7c-5p to upregulate THBS1. These findings highlighted its potential as a prognostic biomarker.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163054","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":"MiR-766-3P promotes degenerative lumbar disc disease by regulating SIRT6 to aggravate the inflammatory response of human nucleus pulposus cells.","authors":"Dongwei An, Pan Yang","doi":"10.1186/s41065-026-00696-5","DOIUrl":"10.1186/s41065-026-00696-5","url":null,"abstract":"<p><strong>Background: </strong>Lumbar degenerative disc disease (LDD) is a disabling condition which was associated with progressive degeneration of the intervertebral discs. The miR-766-3p and its modulation of SIRT6 remains unclear in LDD.</p><p><strong>Purpose: </strong>This study aims to explored the regulated function of miR-766-3p and SIRT6 during LDD.</p><p><strong>Methods: </strong>Human nucleus pulposus cells (HNPCs) were treated with lipopolysaccharide (LPS) to construct a model of LDD to simulate inflammatory conditions. RT-qPCR and ELISA assays were employed to measure the expression of miR-766-3p and SIRT6. Additionally, we evaluated the levels of TNF‑α, IL‑1β, IL‑6, aggrecan, and collagen II by ELISA. Dual-luciferase reporter assays validated direct targeting between miR-766-3p and SIRT6.</p><p><strong>Results: </strong>We observed that miR-766-3p was upregulated in LDD patients, and SIRT6 was downregulated. It is consistent with the changes in LPS-induced HNPCs. Additionally, when we inhibited the miR-766-3p and overexpressed SIRT6, inflammatory cytokines decreased, whereas aggrecan and collagen II increased. Moreover, the inhibition of miR-766-3p increased SIRT6, which was decreased by LPS. And the binding relationship between miR-766-3p and SIRT6 was confirmed by luciferase activity. MiR-766-3p mimic reversed the effects of elevated SIRT6 expression.</p><p><strong>Conclusion: </strong>The findings identify the miR-766-p/SIRT6 axis as a critical regulator mediating inflammatory responses and driving extracellular matrix degradation during LDD. Targeting this molecular pathway would offer novel therapeutic strategies for mitigating tissue damage of LDD.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149669","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":"TLE1 as a key regulator of osimertinib resistance and EMT in lung adenocarcinoma: implications for prognosis and immunotherapy response.","authors":"Na Chen, Tianlin Wang, Yi Li, Ruixia Zhang, Xiduan Wei, Zhenglu Wang","doi":"10.1186/s41065-026-00690-x","DOIUrl":"10.1186/s41065-026-00690-x","url":null,"abstract":"<p><strong>Background: </strong>Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) poses a considerable challenge for the long-term treatment of non-small cell lung cancer (NSCLC). This study aims to identify a novel biomarker associated with osimertinib resistance and explore its role in EGFR-TKI resistance in lung adenocarcinoma (LUAD).</p><p><strong>Methods: </strong>Comprehensive bioinformatics analysis were done using transcriptomic data from the TCGA and GEO databases to identify genes associated with osimertinib tolerance. Candidate genes were further screened against a histone modification-related gene set from MSigDB, leading to the identification of TLE1. The hub gene, TLE1, was further evaluated through survival analysis, GSEA and CIBERSORT analyses. Loss-of-function experiments performed in vitro were utilized to assess the impact of TLE1 on osimertinib resistance in LUAD.</p><p><strong>Results: </strong>TLE1 was of particularly noteworthy, exhibiting elevated expression in LUAD, especially in stage IV patients, and was associated with poor prognosis. GSEA results showed that mTOR, VEGF and HIF-1 signaling pathways were notably activated in the high TLE1 expression group. CIBERSORT analysis markedly elevated levels of regulatory T cells (Tregs) in the TLE1 high expression group. Additionally, epithelial-mesenchymal transition (EMT) scores were significantly elevated in osimertinib tolerant groups and exhibited a positive correlation with TLE1 expression. Furthermore, TLE1 expression was significantly higher in osimertinib-resistant PC9 cells compared to parental PC9 cells. Downregulation of TLE1 enhanced the sensitivity of osimertinib-resistant PC9 cells to osimertinib.</p><p><strong>Conclusions: </strong>TLE1 was identified as a critical gene associated with osimertinib tolerance, influencing LUAD progression, potentially serving as a novel therapeutic target.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054340","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":"Targeted knockout of barley Ycf54 demonstrates its essential function in the Mg-protoporphyrin IX monomethyl ester cyclase involved in chlorophyll biosynthesis.","authors":"Helmy M Youssef, Iris Hoffie, Otto Nordling, David Stuart, Shakhira Zakhrabekova, Radwa Y Helmi, Jochen Kumlehn, Mats Hansson","doi":"10.1186/s41065-026-00693-8","DOIUrl":"10.1186/s41065-026-00693-8","url":null,"abstract":"<p><strong>Background: </strong>The Mg-protoporphyrin IX monomethyl ester cyclase is one of the 15 enzymes required for biosynthesis of chlorophyll in plants. The Ycf54 protein is a component associated with this enzyme and probably functions as a chaperone. Due to the lack of mutants in the Ycf54 gene, we targeted this gene in barley (Hordeum vulgare L.) by RNA-guided Cas9 genome editing to dissect its role in chlorophyll biosynthesis.</p><p><strong>Results: </strong>Two guide RNAs were designed and delivered via Agrobacterium-mediated transformation. We generated four homozygous mutant alleles harboring deletions of 1, 2, 6 and 27 base pairs. The 27 bp deletion mutant also had a silent C-to-G point mutation before the deletion and a CC-to-AG mutation following the deletion changing a serine residue to glutamate. The mutants exhibited three distinct phenotypes: completely yellow leaves, green leaves with yellow stripes, and fully green leaves. Yellow-leafed plants were classified as Xantha mutants, characterized by an absence of chlorophyll but presence of carotenoids. The striped phenotype represented chimeric individuals with severe mutations in meristematic tissues. Yellow mutants carried homozygous 1 or 2 bp deletions, both of which caused translational reading frame shifts and premature truncation of the Ycf54 protein, likely disrupting chlorophyll biosynthesis and resulting in lethality. These mutations could only be stored in heterozygous lines. In contrast, the 6 and 27 bp deletions were in-frame and did not have any observed effect on the green phenotype, demonstrating that these mutations, and the CC-to-AG mutation, preserve Ycf54 functionality with maintained chlorophyll synthesis and plant viability.</p><p><strong>Conclusions: </strong>Previous studies have implicated Ycf54 in the folding and maturation of the cyclase enzyme. Our findings provide direct genetic evidence that Ycf54 is essential for chlorophyll biosynthesis. Loss-of-function mutations result in a lethal, chlorophyll-deficient phenotype, underscoring the critical role of Ycf54 in photosynthetic development.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13221752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054383","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":"miR-4513 promotes the proliferation and metastasis of non-small cell lung cancer cells by targeting VIPR1.","authors":"Zhonghao Pang, Bing Huang, Ying Cui, Shanwu Ma, Bin Zheng, Xuhua Zhang, Ying Liu","doi":"10.1186/s41065-026-00688-5","DOIUrl":"10.1186/s41065-026-00688-5","url":null,"abstract":"<p><strong>Objectives: </strong>The pathogenesis of non-small cell lung cancer (NSCLC) is complex. This research focuses on the expression, function, and molecular mechanisms of miR-4513 in NSCLC.</p><p><strong>Method: </strong>A total of 126 matched tissue pairs (NSCLC and adjacent normal) were collected, along with assessment of miR-4513 and VIPR1 expression in multiple cell lines (A549, H1299, BEAS-2B) by qRT-PCR. In vitro, the influence of miR-4513 on cellular phenotypes was assessed by determining proliferation rates through CCK-8 assay and quantifying migration/invasion capacities via Transwell systems. Targetscan predicted the targeting relationship between miR-4513 and VIPR1, which was subsequently confirmed by dual-luciferase.</p><p><strong>Results: </strong>The expression of miR-4513 is upregulated in NSCLC tissues. The high expression of miR-4513 is associated with pathological features. Survival analysis revealed that high expression of miR-4513 was an independent predictor of unfavorable clinical outcomes in NSCLC patients. In vitro, overexpression of miR-4513 can promote the proliferation, migration and invasion of NSCLC cells, while inhibition of its expression has the opposite effect. VIPR1 overexpression significantly inhibited the proliferation and invasion of NSCLC cells, confirming its tumor-suppressive role. Furthermore, miR-4513 can directly bind to the 3'UTR region of the VIPR1 gene and show a negative correlation with it.</p><p><strong>Conclusions: </strong>High expression of miR-4513 may serve as a potential biomarker for poor prognosis in NSCLC patients. In addition, miR-4513 may promote the malignant progression of NSCLC by targeting VIPR1.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054331","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":"Identification and validation of biomarkers associated with mitotic catastrophe in high-altitude hypoxia.","authors":"Wenwen Zhao, Defang Liu, Ting Luo, Yang Wu","doi":"10.1186/s41065-026-00692-9","DOIUrl":"https://doi.org/10.1186/s41065-026-00692-9","url":null,"abstract":"<p><strong>Background: </strong>High-altitude hypoxia (HAH) can cause adverse reactions, such as tinnitus and barotrauma, but the role of mitotic catastrophe (MC) in HAH remains unreported. This study investigated MC-associated biomarkers in HAH.</p><p><strong>Methods: </strong>HAH-related datasets and MC-related genes (MC-RGs) were retrieved from public databases. Differentially expressed genes (DEGs) between the HAH and control groups were screened, and overlapping genes between DEGs and MC-RGs were defined as candidates. Biomarkers were identified using three machine learning methods, receiver operating characteristic curve analysis, and expression validation. A nomogram was constructed for diagnostic assessment. Functional enrichment, immune infiltration, regulatory network, and drug prediction analyses were performed, with biomarker expression verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>DIAPH1 and MDM4 were confirmed as MC-associated biomarkers in HAH, and the nomogram displayed excellent diagnostic ability (area under the curve = 0.929). These biomarkers were coenriched in pathways such as oxidative phosphorylation. DIAPH1 was positively correlated with the infiltration of resting NK cells, whereas MDM4 was negatively correlated with that of M2 macrophages. A transcription factor-mRNA-miRNA network was established, with USF2 and GATA2 jointly targeting both biomarkers. Drugs such as rescinnamine targeted MDM4. RT-qPCR verified that USF2 and GATA2 were significantly downregulated in HAH (both P < 0.01), consistent with the bioinformatics results.</p><p><strong>Conclusions: </strong>DIAPH1 and MDM4 are valid MC-associated biomarkers for HAH. This study provides novel insights into HAH prevention and treatment.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of lactylation-related genes signature and immune infiltration landscape of rheumatoid arthritis based on machine learning.","authors":"Xiaoli Hu, Qian Xiao, Lizhou Wang, Yuan Xu, Qiaoqiao Gou, Jing Wen, Shi Zhou","doi":"10.1186/s41065-025-00579-1","DOIUrl":"10.1186/s41065-025-00579-1","url":null,"abstract":"<p><strong>Background: </strong>The pathogenic mechanisms underlying rheumatoid arthritis (RA) remain elusive. Lactylation, a novel post-translational modification, may regulate immune and metabolic reprogramming, underscoring the imperative to delineate lactylation-related genes (LRGs) driving RA progression.</p><p><strong>Methods: </strong>LRG expression profiles from RA patients and healthy controls were analyzed from GEO datasets. Immune infiltration and LRG-immune correlations were assessed. A machine-learning framework identified a hub LRG signature, whose metabolic and therapeutic relevance was evaluated via functional enrichment and druggability analyses. qRT-PCR validated hub gene expression in RA MH7A cells model.</p><p><strong>Results: </strong>Transcriptomic profiling identified 36 differentially expressed LRGs regulating cytokine networks and immune signaling in RA. Disease stratification revealed two molecular subtypes, with Subtype B demonstrating p53 signaling and innate immunity pathway activation via gene set variation analysis (GSVA). Weighted correlation network analysis (WGCNA) identified subtype B-associated modules (504 genes). A machine learning-derived 7-LRG signature (Sdc1, Pfkfb1, Fut8, Adh1b, Kif23, Adh1c, Pkc1) differentiated RA from controls (AUC 0.92). Single-cell resolution analysis localized Sdc1 to plasma cell clusters, correlating with memory B cell expansion and macrophage polarization. Hub LRGs were enriched in glucose metabolism pathways in RA, and Sdc1, Adh1b, and Adh1c were druggable, suggesting potential therapeutic targets. qRT-PCR validation confirmed significant LRG upregulation in RA cellular models.</p><p><strong>Conclusion: </strong>Our findings establish lactylation as a key modulator of immune dysregulation in RA pathogenesis. Seven LRG biomarkers were identified and validated, exhibiting dual potential as prognostic indicators and therapeutic targets through lactylation-driven pathway modulation for RA.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941147","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":"LncRNA HOXA11-AS promotes idiopathic pulmonary fibrosis progression via sponging miR-148a-3p and regulating SMAD2.","authors":"Lidong Wang, Xing Ding, Ran Tang, Heping Jiang","doi":"10.1186/s41065-026-00684-9","DOIUrl":"10.1186/s41065-026-00684-9","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic Pulmonary Fibrosis (IPF) is characterized primarily by progressive lung tissue scarring. This study aimed to explore the molecular mechanism of the HOXA11-AS/miR-148a-3p/SMAD2 axis in IPF.</p><p><strong>Methods: </strong>Sixty IPF patients and 70 healthy controls were recruited. mRNA expression was measured by RT-qPCR. An IPF model was established in A549 cells and MRC-5 cells using transforming growth factor-beta 1 (TGF-β1) induction. Cell proliferation, apoptosis, oxidative stress levels, and fibrosis markers were assessed using the cell counting kit-8 (CCK-8), flow cytometry, and enzyme-linked immunosorbent assay (ELISA), respectively. A dual-luciferase reporter assay was conducted to confirm the regulatory interaction.</p><p><strong>Results: </strong>In IPF patients, HOXA11-AS expression was significantly upregulated. Its expression was negatively correlated with lung function parameters as well as with the 6-minute walk test (6MWT) distance. Conversely, it was positively associated with fibrosis-related serum markers, such as hyaluronic acid (HA) and laminin (LN). These findings suggested that HOXA11-AS may serve as a promising diagnostic biomarker for IPF. Moreover, HOXA11-AS promoted the proliferation, suppressed apoptosis, enhanced oxidative stress by reducing superoxide dismutase (SOD) activity and increasing malondialdehyde (MDA) levels, and upregulated the key fibrosis markers expression, including alpha-smooth muscle actin (α-SMA), Collagen I, and Fibronectin. HOXA11-AS directly binds to miR-148a-3p, which in turn targets and regulates SMAD2. Notably, inhibition of miR-148a-3p reversed the suppressive effects of HOXA11-AS knockdown on TGF-β1-induced proliferation, oxidative stress, and fibrotic phenotypes in A549 cells, while restoring SMAD2 expression. Consistent results were observed in MRC-5 fibroblasts: HOXA11-AS knockdown significantly attenuated TGF-β1-induced proliferation, promoted apoptosis, and decreased the expression of α-SMA, Collagen I, and Fibronectin. These effects were partially reversed by miR-148a-3p inhibition, confirming the functional role of the HOXA11-AS/miR-148a-3p/SMAD2 axis in lung fibroblasts.</p><p><strong>Conclusions: </strong>HOXA11-AS promoted the IPF progression by upregulating SMAD2 expression through the sponging of miR-148a-3p.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941246","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":"MiR-642a-3p increases the risk of postmenopausal osteoporosis and fractures by targeting INO80.","authors":"Jingyu Zhang, Han Xiao","doi":"10.1186/s41065-026-00689-4","DOIUrl":"10.1186/s41065-026-00689-4","url":null,"abstract":"<p><strong>Background: </strong>Postmenopausal osteoporosis (PMO), a metabolic bone disorder from estrogen deficiency, disrupts the balance between bone resorption and formation. Its severe consequence, osteoporotic fractures (OPF), significantly increases disability and mortality, severely impacting patients' quality of life. Elevated miR-642a-3p has been identified in both PMO and bone loss. This research aims to further explore the role of miR-642a-3p in predicting PMO development and OPF risk, along with its underlying mechanisms.</p><p><strong>Results: </strong>The research enrolled 127 PMO patients and 91 healthy volunteers (HV). And further subdivided the PMO group into osteoporotic fractures (n = 62) subgroup and without fractures (OPNF, n = 65) subgroup. The results indicate that miR-642a-3p was significantly upregulated in both the PMO and OPF groups. MiR-642a-3p demonstrated good predictive performance for PMO occurrence and OPF risk. High miR-642a-3p expression was identified as an independent risk factor for progression from PMO to OPF. Downregulation of miR-642a-3p not only stimulated osteoblast proliferation but also mitigated associated inflammation and oxidative stress. Furthermore, INO80 is targeted and regulated by miR-642a-3p.</p><p><strong>Conclusion: </strong>MiR-642a-3p may have potential as a biomarker for future clinical prediction of PMO and OPF. Inhibition of miR-642a-3p promotes osteoblast proliferation, associated inflammation, and oxidative stress by upregulation of INO80 expression.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928697","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}