Hereditas最新文献

{"title":"Identification of anoikis-related genes in heart failure: bioinformatics and experimental validation.","authors":"Lina Zhang, Jianjun Gu, Yan Jiang, Juan Xue, Ye Zhu","doi":"10.1186/s41065-025-00532-2","DOIUrl":"10.1186/s41065-025-00532-2","url":null,"abstract":"<p><strong>Background: </strong>Heart failure (HF) is a common clinical syndrome caused by ventricular dysfunction and one of the leading causes of mortality worldwide. Previous studies have suggested that anoikis is relevant to HF. This study aimed to identify hub genes associated with anoikis that may offer therapeutic targets for HF.</p><p><strong>Materials and methods: </strong>Gene expression data for GSE36074 were obtained from the Gene Expression Omnibus (GEO) and anoikis-related genes (ARGs) were extracted from GeneCards. GEO2R was used to screen for differentially expressed genes (DEGs), then by overlapping DEGs with ARGs, differentially expressed ARGs (DEARGs) were screened. The biological functions of the DEARGs were determined using DAVID. Subsequently, two machine learning (ML) algorithms were employed to identify hub DEARGs: least absolute shrinkage and selection operator (LASSO) and random forest (RF). In addition, miRNA-hub DEARGs and drug-hub DEARGs networks were constructed. Lastly, the hub DEARGs were validated by quantitative reverse transcription PCR (RT-qPCR) and Immunofluorescence (IF).</p><p><strong>Results: </strong>A total of 138 DEARGs were identified in GSE36074. Functional analysis of DEARGs revealed that they were primarily enriched in the positive regulation of the apoptotic process, PI3K-Akt, and FoxO signaling pathways. Subsequently, two hub DEARGs (Tln1 and TGFβ2) were screened using LASSO and RF algorithms. According to the miRNA-hub DEARGs networks, Tln1 and TGFβ2 were regulated by 34 and 68 miRNAs, respectively. Moreover, drug-hub DEARGs networks showed that Gemogenovatucel-t, Lerdelimumab, Belagenpumatucel-l, Fresolimumab, Bintrafusp alfa, Trabedersen and Luspatercept-aamt are potential drugs that could target TGFβ2. Finally, RT-qPCR and IF validation of two key DEARGs (Tln1 and TGFβ2) supported our bioinformatics analysis.</p><p><strong>Conclusions: </strong>These findings suggest that Tln1 and TGFβ2 may play important roles in HF development through the regulation of anoikis and may serve as therapeutic targets for HF.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"163"},"PeriodicalIF":2.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862189","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":"Programmed death 1 inhibitor combined with radiotherapy decreases epidermal growth factor receptor expression in breast cancer.","authors":"You Wu","doi":"10.1186/s41065-025-00472-x","DOIUrl":"10.1186/s41065-025-00472-x","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effect of programmed death 1 (PD-1) inhibitors combined with radiotherapy on the expression of P53 and epidermal growth factor receptor (EGFR) in breast cancer (BC). The impact of radiation treatment on BC patients' prognosis was examined.</p><p><strong>Methods: </strong>The data of BC patients admitted to Nanjing University of Chinese Medicine from April 2022 to April 2023 were retrospectively analyzed. The clinical data of the patients were extracted, and 104 patients were randomly enrolled. The survival time and complications of patients were followed up. The expression levels of P53 and EGFR in tumor tissues and prognosis of patients treated with PD-1 inhibitor combined with radiotherapy were analyzed.</p><p><strong>Result: </strong>The expression level of EGFR in the joint group (JG) was visibly lower as against the control group (CG); The median progression-free survival (PFS) of the JG was visibly longer as against the CG (all P < 0.05). The optimal cut-off values of P53 positive rate and EGFR level before combined treatment were 10% and 96.21ng/mL. In addition, the median PFS of individuals with low EGFR in the JG was 7.3, which was visibly higher as against individuals with high EGFR. The level of EGFR before PD-1 inhibitor treatment was an independent cause of risk affecting the prognosis of patients.</p><p><strong>Conclusion: </strong>PD-1 inhibitor plus radiotherapy can effectively inhibit the expression of EGFR in tumor tissues of BC patients and visibly improve the prognosis.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"160"},"PeriodicalIF":2.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862191","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":"Multi-omics approach reveals CCND1, GABPA, HIF1A, and SOX6 as key regulators and prognostic markers in heart failure.","authors":"Ping He, Lang Deng, Kaijie Wu","doi":"10.1186/s41065-025-00536-y","DOIUrl":"10.1186/s41065-025-00536-y","url":null,"abstract":"<p><strong>Introduction: </strong>Heart failure (HF) is a progressive condition with complex molecular mechanisms. This study aims to identify potential biomarkers and therapeutic targets by analyzing differentially expressed genes (DEGs) in HF patients, exploring the roles of hub genes, and developing a risk model for predicting disease progression.</p><p><strong>Methodology: </strong>We cultured five human HF cell lines and five normal coronary cardiomyocyte cell lines. Gene expression datasets were retrieved from the Gene Expression Omnibus (GEO) database and analyzed using limma. Protein-Protein Interaction (PPI) networks were constructed with STRING, and immune cell infiltration was analyzed using CIBERSORT. A risk model was built using LASSO regression. Drug screening was performed via CMap, and overexpression studies of CCND1 and HIF1A were conducted in AC16 and SEKHEP1 cells via cell proliferation, colony formation, and wound healing assays.</p><p><strong>Results: </strong>We identified 182 common DEGs associated with HF. Hub genes CCND1, GABPA, HIF1A, and SOX6 were central in the PPI network. LASSO regression established a risk model linked to disease progression. Immune infiltration analysis revealed altered immune cell profiles in HF. The miRNA-mRNA network showed interactions of hsa-miR-93-5p, hsa-miR-802, hsa-miR-199a-5p, and hsa-miR-203a-3p with hub genes. Overexpression of CCND1 and HIF1A in cell lines impaired proliferation, colony formation, and migration, implicating their role in HF pathophysiology.</p><p><strong>Conclusion: </strong>CCND1, GABPA, HIF1A, and SOX6 may serve as biomarkers for HF. Our findings provide valuable insights into immune infiltration, miRNA regulation, and the identification of therapeutic targets for HF management. These results highlight the role of gene regulation in HF progression and may guide future therapeutic interventions.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"165"},"PeriodicalIF":2.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862190","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":"β-Nicotinamide mononucleotide alleviates Alcohol-Induced liver injury in a mouse model through activation of NAD⁺/SIRT1 signaling pathways.","authors":"Xinxin Yang, Endian Zheng, Yuxian Lin, Haoyue Sun, Ji Zhang, Yingcong Yu","doi":"10.1186/s41065-025-00529-x","DOIUrl":"10.1186/s41065-025-00529-x","url":null,"abstract":"<p><strong>Background: </strong>Alcoholism is a significant contributor to the development of alcoholic liver disease, for which no universally accepted and effective treatment currently exists. A precursor of NAD⁺, β-Nicotinamide mononucleotide (NMN), has revealed potential therapeutic benefits. However, its effectiveness in preventing ethanol-induced liver damage remains uncertain.</p><p><strong>Methods: </strong>The objective of this study was to assess the protective effects of NMN and elucidate its potential mechanisms using a mouse model subjected to chronic and binge ethanol feeding. Eight-week-old C57BL/6J mice were randomly assigned to one of four groups (n = 10 per group): control (CTRL), ethanol (EtOH), ethanol with low-dose NMN (EtOH + NMN(L)), and ethanol with high-dose NMN (EtOH + NMN(H)). Following the completion of the experimental protocol, the mice were euthanized at designated time points, and blood, liver, and ileum tissues were collected for analysis of relevant biomarkers.</p><p><strong>Results: </strong>Compared to the CTRL group, the EtOH group demonstrated increased liver specific gravity and elevated blood ALT levels. Administration of NMN improved histopathological changes in the liver and ileum of the mice. NMN significantly counteracted the ethanol-induced elevation in liver MDA levels and restored the diminished glutathione (GSH) and superoxide dismutase (SOD) activity levels caused by ethanol exposure. Additionally, NMN inhibited the ethanol-induced expression of cytochrome P450 2E1 (CYP2E1). It also reduced the release of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, which were triggered by ethanol exposure, improved energy homeostasis in the ileum, and reversed the downregulation of mRNA and protein expression of key tight junction proteins in the ileum, specifically ZO-1, Claudin-1, and Occludin, thereby restoring their functional integrity. Furthermore, NMN activated the NAD⁺/ SIRT1 signaling pathway, leading to the upregulation of all target genes.</p><p><strong>Conclusion: </strong>NMN supplementation provides protection against alcoholic liver injury in a mouse model, potentially through the upregulation of the cellular NAD⁺/ SIRT1 pathway. This upregulation enhances antioxidant and anti-inflammatory activities and improves intestinal permeability.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"161"},"PeriodicalIF":2.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862192","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":"Global trends in machine learning applications for single-cell transcriptomics research.","authors":"Xinyu Liu, Zhen Zhang, Chao Tan, Yinquan Ai, Hao Liu, Yuan Li, Jin Yang, Yongyan Song","doi":"10.1186/s41065-025-00528-y","DOIUrl":"10.1186/s41065-025-00528-y","url":null,"abstract":"<p><strong>Background: </strong>Single-cell RNA sequencing (scRNA-seq) has revolutionized cellular heterogeneity analysis by decoding gene expression profiles at individual cell level, while machine learning (ML) has emerged as core computational tool for clustering analysis, dimensionality reduction modeling and developmental trajectory inference in single-cell transcriptomics(SCT). Although 3,307 papers have been published in past two decades, there remains lack of bibliometric review comprehensively addressing methodological evolution, technical challenges and clinical translation pathways. This study aims to fill research gap through bibliometric and visual analysis, revealing technological evolution trends and future development directions.</p><p><strong>Methods: </strong>Using 3,307 publications from Web of Science Core Collection(WOSCC), we conducted bibliometric and visualization analysis through CiteSpace and VOSviewer to systematically review research trends, national/institutional contributions, keyword co-occurrence networks and co-citation relationships. Data screening strictly limited to English articles and reviews, excluding irrelevant document types, focusing on core application scenarios of ML in SCT.</p><p><strong>Results: </strong>China and United States dominated research output (combined 65%), with China leading in publication volume (54.8%) while US demonstrating academic influence through H-index 84 and 37,135 total citations. Research hotspots concentrated on random forest (RF) and deep learning models, showing transition from algorithm development to clinical applications (e.g., tumor immune microenvironment analysis). Chinese Academy of Sciences and Harvard University emerged as core collaboration hubs, with international cooperation network primarily featuring US-China collaboration. Keyword clustering revealed four themes: gene expression, immunotherapy, bioinformatics, and inflammation-related research. Technical bottlenecks included data heterogeneity, insufficient model interpretability and weak cross-dataset generalization capability.</p><p><strong>Conclusion: </strong>ML-scRNA-seq integration has advanced cellular heterogeneity analysis and precision medicine development. Future directions should optimize deep learning architectures, enhance model generalization capabilities, and promote technical translation through multi-omics and clinical data integration. Interdisciplinary collaboration represents key to overcoming current limitations (e.g., data standardization, algorithm interpretability), ultimately realizing deep integration between single-cell technologies and precision medicine.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"164"},"PeriodicalIF":2.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862241","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":"A comprehensive in silico and invitro analysis revealed the diagnostic, prognostic and therapeutic potential of GNAI family genes in colon adenocarcinoma (COAD).","authors":"Bei Wang, Fan Zhu, Yingying Chen","doi":"10.1186/s41065-025-00523-3","DOIUrl":"10.1186/s41065-025-00523-3","url":null,"abstract":"","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"162"},"PeriodicalIF":2.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862240","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":"COL1A1, ITGB1, THY1, and PDGFRA: key immune-related genes in uterine corpus endometrial carcinoma with prognostic and therapeutic implications.","authors":"Taghreed N Almanaa, Abdulaziz Alamri, Mostafa A Abdel-Maksoud, Ibrahim A Saleh, Naser Zomot, Jehad S Al-Hawadi, Wahidah H Al-Qahtani, Yasir Hameed","doi":"10.1186/s41065-025-00448-x","DOIUrl":"10.1186/s41065-025-00448-x","url":null,"abstract":"<p><p>Uterine corpus endometrial carcinoma (UCEC) is one of the most common gynecological malignancies, characterized by complex molecular alterations that drive its progression. Understanding the molecular mechanisms underlying UCEC is crucial for developing effective diagnostic, prognostic, and therapeutic strategies. Immune-related genes, such as COL1A1, ITGB1, THY1, and PDGFRA, have been implicated in various cancers, but their roles in UCEC remain underexplored. In this study, we investigate the roles of these genes in the development and progression of UCEC. Using both in silico and in vitro approaches, we found that these genes were dysregulated in UCEC. Our results revealed the downregulation of COL1A1, ITGB1, THY1, and PDGFRA in UCEC compared to normal tissues. Further, promoter methylation analysis showed increased methylation of these genes in UCEC. Survival analysis highlighted their potential as prognostic markers, with lower expression linked to poor patient survival. Additionally, genetic alteration analysis demonstrated mutations in these genes across UCEC patients. Our results also showed that overexpression of COL1A1 in KLE and HEC-1B cells significantly reduced cell proliferation, colony formation, and migration, indicating that COL1A1 overexpression impacts critical cellular behaviors in UCEC. Finally, we explored the therapeutic potential of targeting these genes, suggesting that they may offer valuable insights for personalized treatment strategies in UCEC. This study identifies COL1A1, ITGB1, THY1, and PDGFRA as crucial regulators of UCEC progression, with altered expression linked to tumor behavior and patient survival. Overexpression of COL1A1 impaired cell proliferation, colony formation, and migration. Future research should focus on elucidating the molecular mechanisms of these genes, exploring their therapeutic targeting in preclinical models, and validating their clinical potential as biomarkers in larger patient cohorts to improve treatment strategies for UCEC.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"159"},"PeriodicalIF":2.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859125","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":"USP8 protects rat-derived H9C2 cardiomyocytes from doxorubicin-triggered ferroptosis and cell death through deubiquitination-mediated stabilization of MDM4.","authors":"Yixi Li, Xue Yang, Liang Zhang","doi":"10.1186/s41065-025-00527-z","DOIUrl":"10.1186/s41065-025-00527-z","url":null,"abstract":"<p><strong>Background: </strong>Acute heart failure (AHF) is a life-threatening clinical syndrome due to impaired cardiac function. Ferroptosis has emerged as a contributor to cytotoxicity in cardiomyocytes. However, the functional interplay between USP8 and ferroptosis during AHF has not been investigated.</p><p><strong>Methods: </strong>H9C2 rat cardiomyocytes were treated with doxorubicin (Dox) to establish an experimental model. Cell cytotoxicity was evaluated by measuring cell viability, LDH release, and cell death. Ferroptosis was assessed by analyzing Fe²⁺, lipid ROS, MDA, and GSH levels in treated cells. Immunoprecipitation (IP), Co-IP, and protein stabilization assays were performed to validate the USP8/murine double minute 4 (MDM4) interaction and the regulation of USP8 in MDM4. Expression of mRNA and protein was quantified by quantitative PCR and immunoblot analyses, respectively.</p><p><strong>Results: </strong>USP8 and MDM4 were downregulated in Dox-exposed H9C2 cardiomyocytes. USP8 overexpression alleviated Dox-triggered cytotoxicity and cell death in H9C2 cardiomyocytes. Moreover, USP8 overexpression mitigated H9C2 cardiomyocyte ferroptosis induced by Dox. Mechanistically, USP8 stabilized MDM4 via deubiquitination. Inhibition of MDM4 counteracted the ability of USP8 overexpression to attenuate Dox-triggered cell death and ferroptosis in H9C2 cardiomyocytes.</p><p><strong>Conclusion: </strong>Our findings indicate that USP8 overexpression protects H9C2 cardiomyocytes from Dox-induced ferroptosis by stabilizing MDM4 via deubiquitination.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"158"},"PeriodicalIF":2.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855092","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":"Clinical efficacy of acupoint application therapy combined with Kangyou Decoction in treating Helicobacter pylori infection with damp-heat syndrome of the middle Jiao.","authors":"Shang-Ren Xie, Meng-Yi Lv, Jun Yang, Hai-Jing Chen, Jie-Ru Wu, Yao-Qi Xu, Jie Jin, Jian-Wei Jin","doi":"10.1186/s41065-025-00533-1","DOIUrl":"10.1186/s41065-025-00533-1","url":null,"abstract":"<p><strong>Background: </strong>This study evaluated the clinical efficacy and safety of acupoint application of traditional Chinese medicine (TCM) combined with Kangyou Decoction in patients with Helicobacter pylori (Hp) infection presenting with damp-heat syndrome obstructing the middle jiao.</p><p><strong>Methods: </strong>A total of 416 patients with Hp infection and TCM-defined damp-heat syndrome of the middle jiao were enrolled and randomly assigned to a treatment group (n = 208) or a control group (n = 208). The control group received standard bismuth-containing quadruple therapy, while the treatment group received acupoint application of TCM combined with oral administration of Kangyou Decoction. Both groups underwent treatment for two weeks. Outcomes included Hp eradication rates, changes in TCM syndrome scores pre- and post-treatment, and the incidence of adverse reactions.</p><p><strong>Results: </strong>Following two weeks of therapy, no statistically significant difference in Hp eradication rates was observed between the two groups (p > 0.05). Both groups demonstrated significant improvement in TCM syndrome scores (p < 0.05), with the treatment group showing a greater reduction compared to the control group (p < 0.05). The total effective rate in the treatment group was higher than that in the control group. Incidences of adverse reactions did not differ significantly between the groups (p > 0.05).</p><p><strong>Conclusion: </strong>Acupoint application combined with Kangyou Decoction yielded comparable Hp eradication outcomes to bismuth quadruple therapy in patients with damp-heat syndrome of the middle jiao. The combined therapy demonstrated greater improvement in clinical symptoms with a favorable safety profile, supporting its potential for clinical application.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"157"},"PeriodicalIF":2.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855090","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":"TFAP2A promotes NSCLC malignant progression by enhancing AOC1 transcription.","authors":"Xiang Miao, Hongzhen Zheng, Huimin Mo, Jing Chang, Qin Jia, Hai Zhou","doi":"10.1186/s41065-025-00524-2","DOIUrl":"10.1186/s41065-025-00524-2","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) has high mortality, and patients show variable outcomes and drug responses. Amine oxidase copper-containing 1 (AOC1) is considered an oncogene in many types of tumors. Transcription factor AP-2 alpha (TFAP2A) can affect a variety of biological processes and play a crucial role in driving tumorigenesis and tumor development. Consequently, this work is designed to delve into the effects of AOC1 and TFAP2A on NSCLC progression.</p><p><strong>Methods: </strong>Bioinformatics analysis was employed to analyze AOC1 and TFAP2A expression in the TNMplot database and the survival significance of high- or low-expression of AOC1 in NSCLC patients. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot were implemented to assay the mRNA and protein expression levels of genes. Cell proliferation, migration, and apoptosis were detected using 5-ethynyl-2'-deoxyuridine (EdU), wound healing, and flow cytometry, respectively. In addition, mitochondrial membrane potential and reactive oxygen species (ROS) were examined using JC-1 and ROS detection kits. The macrophage M2 polarization was tested via flow cytometry. The construction of subcutaneous transplanted tumors in nude mice confirmed the effect of AOC1 in vivo. In order to discern the upstream regulatory mechanisms, the JASPAR database was utilized to predict the transcription factors and binding sites associated with AOC1. Chromatin immunoprecipitation (CHIP) and luciferase reporter gene assays were performed to solidify the binding relationship between AOC1 and TFAP2A.</p><p><strong>Results: </strong>AOC1 and TFAP2A levels were increased in NSCLC tumor tissues and cell lines (A-549 and NCI-H1299). AOC1 knockdown inhibited NSCLC cell proliferation, migration, M2 macrophage polarization, and mitochondrial membrane potential, and facilitated cell apoptosis and ROS. In vivo, sh-AOC1 suppressed NSCLC tumor growth. Furthermore, TFAP2A facilitated AOC1 expression via transcriptional regulation in NSCLC. Mechanically, TFAP2A promoted NSCLC progression via facilitating AOC1 expression.</p><p><strong>Conclusions: </strong>Silencing TFAP2A inhibits NSCLC progression via regulating AOC1 transcription. Hence, AOC1/TFAP2A may be a feasible therapeutic target for NSCLC.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"156"},"PeriodicalIF":2.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855091","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}