Frontiers in Molecular Biosciences最新文献

{"title":"Editorial: Molecular mechanisms of thrombosis.","authors":"Matteo Becatti, Tom Mckinnon, Claudia Fiorillo, Angelo A Manfredi, Giacomo Emmi","doi":"10.3389/fmolb.2024.1497653","DOIUrl":"10.3389/fmolb.2024.1497653","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399923","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":"Insights into structure and activity of a UDP-GlcNAc 2-epimerase involved in secondary cell wall polymer biosynthesis in <i>Paenibacillus alvei</i>.","authors":"Cordula Stefanović, Max S G Legg, Nick Mateyko, Jakob J Ender, Tea Kuvek, Chris Oostenbrink, Christina Schäffer, Stephen V Evans, Fiona F Hager-Mair","doi":"10.3389/fmolb.2024.1470989","DOIUrl":"10.3389/fmolb.2024.1470989","url":null,"abstract":"<p><strong>Introduction: </strong>S-layer anchoring in <i>Paenibacillus alvei</i> is enabled by a non-covalent interaction between an S-layer homology domain trimer and a secondary cell wall polymer (SCWP), ensuring the structural integrity of the bacterial cell wall. Within the SCWP repeat, pyruvylated ManNAc serves as the ligand and the UDP-GlcNAc-2-epimerase MnaA supplies UDP-ManNAc to SCWP biosynthesis.</p><p><strong>Methods: </strong>To better understand SCWP biosynthesis and identify strategies for inhibiting pathogens with comparable cell wall architecture, like <i>Bacillus anthracis</i>, MnaA and rational variants were produced in <i>E. coli</i> and their kinetic constants determined. The effect of UDP-GlcNAc as a predicted allosteric activator and tunicamycin as a potential inhibitor of MnaA was tested <i>in vitro</i> supported by molecular docking experiments. Additionally, wild-type MnaA was crystallized.</p><p><strong>Results: </strong>We present the crystal structure of unliganded <i>P. alvei</i> MnaA resolved at 2.20 Å. It adopts a GT-B fold consistent with other bacterial non-hydrolyzing UDP-GlcNAc 2-epimerases. A comparison of amino acid sequences reveals conservation of putative and known catalytic and allosteric-site residues in MnaA, which was confirmed through analysis of Q42A, Q69A, E135A and H241A MnaA variants. The kinetic parameters <i>K</i> _M and <i>k</i> _cat of MnaA were determined to be 3.91 mM and 33.44 s^-1 for the forward, and 2.41 mM and 6.02 s^-1 for the reverse reaction. While allosteric regulation by UDP-GlcNAc has been proposed as a mechanism for enzyme activation, UDP-GlcNAc was not found to be essential for UDP-ManNAc epimerization by <i>P. alvei</i> MnaA. However, the reaction rate doubled upon addition of 5% UDP-GlcNAc. Unexpectedly, the UDP-GlcNAc analog tunicamycin did not inhibit MnaA. Molecular docking experiments comparing tunicamycin binding of <i>P. alvei</i> MnaA and <i>Staphylococcus aureus</i> MnaA, which is inhibited by tunicamycin, revealed different residues exposed to the antibiotic excluding, those at the predicted allosteric site of <i>P. alvei</i> MnaA, corroborating tunicamycin resistance.</p><p><strong>Conclusion: </strong>The unliganded crystal structure of <i>P. alvei</i> MnaA reveals an open conformation characterized by an accessible cleft between the N- and C-terminal domains. Despite the conservation of residues involved in binding the allosteric activator UDP-GlcNAc, the enzyme is not strictly regulated by the substrate. Unlike <i>S. aureus</i> MnaA, the activity of <i>P. alvei</i> MnaA remains unaffected by tunicamycin.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399924","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":"Genome-wide association study for growth traits with 1066 individuals in largemouth bass (<i>Micropterus salmoides</i>).","authors":"Wei Han, Ming Qi, Kun Ye, Qiwei He, Dinaer Yekefenhazi, Dongdong Xu, Fang Han, Wanbo Li","doi":"10.3389/fmolb.2024.1443522","DOIUrl":"10.3389/fmolb.2024.1443522","url":null,"abstract":"<p><p>The largemouth bass is a native species of North America that was first introduced to mainland China in the 1980s. In recent years, it has been extensively farmed in China due to its high meat quality and broad adaptability. In this study, we collected growth trait data from 1,066 largemouth bass individuals across two populations. We generated an average of approximately 7× sequencing coverage for these fish using Illumina sequencers. From the samples, we identified 2,695,687 SNPs and retained 1,809,116 SNPs for further analysis after filtering. To estimate the number of genome-wide effective SNPs, we performed LD pruning with PLINK software and identified 77,935 SNPs. Our GWAS revealed 15 SNPs associated with six growth traits. We identified a total of 24 genes related to growth, with three genes-<i>igf1</i>, <i>myf5</i>, and <i>myf6</i>-directly associated with skeletal muscle development and growth, located near the leading SNP on chromosome 23. Other candidate genes are involved in the development of tissues and organs or other physiological processes. These findings provide a valuable set of SNPs and genes that could be useful for genetic breeding programs aimed at enhancing growth in largemouth bass.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389348","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":"Sustainable synthesis of bakuchiol-mediated gold nanoparticles for drug delivery against bacterial strains and tumor microenvironments, and its <i>in silico</i> target proteins identification.","authors":"Pooja Mishra, Tabrez Faruqui, Sheeba Khanam, Mohd Khubaib, Irfan Ahmad, Mohd Saeed, Salman Khan","doi":"10.3389/fmolb.2024.1469107","DOIUrl":"10.3389/fmolb.2024.1469107","url":null,"abstract":"<p><strong>Introduction: </strong>The sustained synthesis of gold nanoparticles (GNPs) has gained significant attention in biomedical applications. In this study, we explored the antibacterial and anticancer potential of bakuchiol-mediated gold nanoparticles (Bak-GNPs). Bakuchiol, a natural compound found in <i>Psoralea corylifolia</i> seeds, serves as both a reducing and stabilizing agent for green synthesis of GNPs. Our objectives include network analysis, molecular docking, synthesis of GNPs, characterization, and antipathogenic and anticancer efficacy of Bak-GNPs against lung and liver cancers.</p><p><strong>Methods: </strong>Protein-protein interaction networks were analyzed to identify effective protein targets for bakuchiol in lung and liver cancers. A molecular docking study was performed to validate the efficacy of the target protein against lung and liver cancer. Furthermore, Bak-GNPs were synthesized using bakuchiol and characterized by various techniques such as UV-visible spectroscopy, dynamic light scattering (DLS), zeta potential transmission electron microscopy (TEM), and Fourier-transform infrared (FTIR) spectroscopy, and their potential against pathogens and lung and liver cancers.</p><p><strong>Results: </strong>GNAI3 emerged as the most promising target, with a binding energy of -7.5 kcal/mol compared to PTGER3's -6.9 kcal/mol, different characterization techniques revealed the successful synthesis of Bak-GNPs. Bak-GNPs exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria, as confirmed by minimum inhibitory concentration (MIC) values. Bak-GNPs demonstrated significant anticancer effects on A549 (lung cancer) and HepG2 (liver cancer) cells, with IC₅₀ values of 11.19 μg/mL and 6.6 μg/mL, respectively. Induction of apoptosis and inhibition of cell proliferation were observed in both the cell lines. The increased production of reactive oxygen species (ROS) contributes to its anticancer effects.</p><p><strong>Discussion: </strong>This study highlights promising biomedical applications of bakuchiol-mediated GNPs. This green synthesis approach using bakuchiol provides a sustainable method for producing nanoparticles with enhanced biological activities. Further exploration of the pharmacological properties and mechanisms of Bak-GNPs is required to optimize their therapeutic efficacy for clinical use.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389349","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":"DNA methylation-mediated <i>FGFR1</i> silencing enhances <i>NF-κB</i> signaling: implications for asthma pathogenesis.","authors":"Minglu Meng, Yingjiao Ma, Jianguo Xu, Gao Chen, Roshan Kumar Mahato","doi":"10.3389/fmolb.2024.1433557","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1433557","url":null,"abstract":"<p><strong>Background: </strong>Fibroblast growth factor receptor 1 (<i>FGFR1</i>) is known to play a crucial role in the pathogenesis of asthma, although the precise mechanism remains unclear. This study aims to investigate how DNA methylation-mediated silencing of <i>FGFR1</i> contributes to the enhancement of NF-κB signaling, thereby influencing the progression of asthma.</p><p><strong>Methods: </strong>RT-qPCR was utilized to assess <i>FGFR1</i> mRNA levels in the serum of asthma patients and BEAS-2B, HBEpiC, and PCS-301-011 cells. CCK8 assays were conducted to evaluate the impact of <i>FGFR1</i> overexpression on the proliferation of BEAS-2B, PCS-301-011, and HBEpiC cells. Dual-luciferase and DNA methylation inhibition assays were performed to elucidate the underlying mechanism of <i>FGFR1</i> gene in asthma. The MassARRAY technique was employed to measure the methylation levels of the <i>FGFR1</i> DNA.</p><p><strong>Results: </strong>Elevated <i>FGFR1</i> mRNA levels were observed in the serum of asthma patients compared to healthy controls. Overexpression of <i>FGFR1</i> in BEAS-2B cells significantly enhanced cell proliferation and stimulated NF-ĸB transcriptional activity in HERK-293T cells. Furthermore, treatment with 5-Aza-CdR, a DNA demethylating agent, markedly increased the expression of <i>FGFR1</i> mRNA in BEAS-2B, PCS-301-011, and HBEpiC cells. Luciferase activity analysis confirmed heightened NF-ĸB transcriptional activity in <i>FGFR1</i>-overexpressing BEAS-2B cells and BEAS-2B cells treated with 5-Aza-CdR. Additionally, a decrease in methylation levels in the <i>FGFR1</i> DNA promoter was detected in the serum of asthma patients using the MassARRAY technique.</p><p><strong>Conclusion: </strong>Our findings reveal a potential mechanism involving <i>FGFR1</i> in the progression of asthma. DNA methylation of <i>FGFR1</i> inactivates the NF-ĸB signaling pathway, suggesting a promising avenue for developing effective therapeutic strategies for asthma.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389347","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":"Screening and identification of the hub genes in severe acute pancreatitis and sepsis.","authors":"Si-Jiu Yang, Yan Luo, Bao-He Chen, Ling-Hui Zhan","doi":"10.3389/fmolb.2024.1425143","DOIUrl":"10.3389/fmolb.2024.1425143","url":null,"abstract":"<p><strong>Background: </strong>Severe acute pancreatitis (SAP) is accompanied with acute onset, rapid progression, and complicated condition. Sepsis is a common complication of SAP with a high mortality rate. This research aimed to identify the shared hub genes and key pathways of SAP and sepsis, and to explore their functions, molecular mechanism, and clinical value.</p><p><strong>Methods: </strong>We obtained SAP and sepsis datasets from the Gene Expression Omnibus (GEO) database and employed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to identify the shared differentially expressed genes (DEGs). Functional enrichment analysis and protein-protein interaction (PPI) was used on shared DEGs to reveal underlying mechanisms in SAP-associated sepsis. Machine learning methods including random forest (RF), least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) were adopted for screening hub genes. Then, receiver operating characteristic (ROC) curve and nomogram were applied to evaluate the diagnostic performance. Finally, immune cell infiltration analysis was conducted to go deeply into the immunological landscape of sepsis.</p><p><strong>Result: </strong>We obtained a total of 123 DEGs through cross analysis between Differential expression analysis and WGCNA important module. The Gene Ontology (GO) analysis uncovered the shared genes exhibited a significant enrichment in regulation of inflammatory response. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the shared genes were primarily involved in immunoregulation by conducting NOD-like receptor (NLR) signaling pathway. Three machine learning results revealed that two overlapping genes (ARG1, HP) were identified as shared hub genes for SAP and sepsis. The immune infiltration results showed that immune cells played crucial part in the pathogenesis of sepsis and the two hub genes were substantially associated with immune cells, which may be a therapy target.</p><p><strong>Conclusion: </strong>ARG1 and HP may affect SAP and sepsis by regulating inflammation and immune responses, shedding light on potential future diagnostic and therapeutic approaches for SAP-associated sepsis.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371486","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":"Exosome-mediated delivery of siRNA molecules in cancer therapy: triumphs and challenges","authors":"Philemon Ubanako, Sheefa Mirza, Paul Ruff, Clement Penny","doi":"10.3389/fmolb.2024.1447953","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1447953","url":null,"abstract":"The discovery of novel and innovative therapeutic strategies for cancer treatment and management remains a major global challenge. Exosomes are endogenous nanoscale extracellular vesicles that have garnered increasing attention as innovative vehicles for advanced drug delivery and targeted therapy. The attractive physicochemical and biological properties of exosomes, including increased permeability, biocompatibility, extended half-life in circulation, reduced toxicity and immunogenicity, and multiple functionalization strategies, have made them preferred drug delivery vehicles in cancer and other diseases. Small interfering RNAs (siRNAs) are remarkably able to target any known gene: an attribute harnessed to knock down cancer-associated genes as a viable strategy in cancer management. Extensive research on exosome-mediated delivery of siRNAs for targeting diverse types of cancer has yielded promising results for anticancer therapy, with some formulations progressing through clinical trials. This review catalogs recent advances in exosome-mediated siRNA delivery in several types of cancer, including the manifold benefits and minimal drawbacks of such innovative delivery systems. Additionally, we have highlighted the potential of plant-derived exosomes as innovative drug delivery systems for cancer treatment, offering numerous advantages such as biocompatibility, scalability, and reduced toxicity compared to traditional methods. These exosomes, with their unique characteristics and potential for effective siRNA delivery, represent a significant advancement in nanomedicine and cancer therapeutics. Further exploration of their manufacturing processes and biological mechanisms could significantly advance natural medicine and enhance the efficacy of exosome-based therapies.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264580","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":"Structural bases for blockade and activation of BK channels by Ba2+ ions","authors":"Shubhra Srivastava, Pablo Miranda, Teresa Giraldez, Jianghai Zhu, Raul E. Cachau, Miguel Holmgren","doi":"10.3389/fmolb.2024.1454273","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1454273","url":null,"abstract":"We studied the impact of Ba<jats:sup>2+</jats:sup> ions on the function and structure of large conductance potassium (BK) channels. Ion composition has played a crucial role in the physiological studies of BK channels due to their ability to couple ion composition and membrane voltage signaling. Unlike Ca<jats:sup>2+</jats:sup>, which activates BK channels through all <jats:italic>Regulator of K</jats:italic><jats:sup><jats:italic>+</jats:italic></jats:sup><jats:italic>Conductance</jats:italic> (RCK) domains, Ba<jats:sup>2+</jats:sup> has been described as specifically interacting with the RCK2 domain. It has been shown that Ba<jats:sup>2+</jats:sup> also blocks potassium permeation by binding to the channel’s selectivity filter. The Cryo-EM structure of the <jats:italic>Aplysia</jats:italic> BK channel in the presence of high concentration Ba<jats:sup>2+</jats:sup> here presented (PDBID: 7RJT) revealed that Ba<jats:sup>2+</jats:sup> occupies the K<jats:sup>+</jats:sup> S3 site in the selectivity filter. Densities attributed to K<jats:sup>+</jats:sup> ions were observed at sites S2 and S4. Ba<jats:sup>2+</jats:sup> ions were also found bound to the high-affinity Ca<jats:sup>2+</jats:sup> binding sites RCK1 and RCK2, which agrees with functional work suggesting that the Ba<jats:sup>2+</jats:sup> increases open probability through the Ca<jats:sup>2+</jats:sup> bowl site (RCK2). A comparative analysis with a second structure here presented (PDBID: 7RK6), obtained without additional Ba<jats:sup>2+</jats:sup>, shows localized changes between the RCK1 and RCK2 domains, suggestive of coordinated dynamics between the RCK ion binding sites with possible relevance for the activation/blockade of the channel. The observed densities attributed to Ba<jats:sup>2+</jats:sup> at RCK1 and RCK2 sites and the selectivity filter contribute to a deeper understanding of the structural basis for Ba<jats:sup>2+</jats:sup>'s dual role in BK channel modulation, adding to the existing knowledge in this field.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264581","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":"Lipid-based nanoparticles: innovations in ocular drug delivery.","authors":"Mirza Salman Baig, Shweta Kulkarni Karade, Anas Ahmad, Mohd Ashif Khan, Anzarul Haque, Thomas J Webster, Md Faiyazuddin, Noora H Al-Qahtani","doi":"10.3389/fmolb.2024.1421959","DOIUrl":"10.3389/fmolb.2024.1421959","url":null,"abstract":"<p><p>Ocular drug delivery presents significant challenges due to intricate anatomy and the various barriers (corneal, tear, conjunctival, blood-aqueous, blood-retinal, and degradative enzymes) within the eye. Lipid-based nanoparticles (LNPs) have emerged as promising carriers for ocular drug delivery due to their ability to enhance drug solubility, improve bioavailability, and provide sustained release. LNPs, particularly solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and cationic nanostructured lipid carriers (CNLCs), have emerged as promising solutions for enhancing ocular drug delivery. This review provides a comprehensive summary of lipid nanoparticle-based drug delivery systems, emphasizing their biocompatibility and efficiency in ocular applications. We evaluated research and review articles sourced from databases such as Google Scholar, TandFonline, SpringerLink, and ScienceDirect, focusing on studies published between 2013 and 2023. The review discusses the materials and methodologies employed in the preparation of SLNs, NLCs, and CNLCs, focusing on their application as proficient carriers for ocular drug delivery. CNLCs, in particular, demonstrate superior effectiveness attributed due to their electrostatic bioadhesion to ocular tissues, enhancing drug delivery. However, continued research efforts are essential to further optimize CNLC formulations and validate their clinical utility, ensuring advancements in ocular drug delivery technology for improved patient outcomes.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361394","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":"The synergistic effects of anoikis-related genes and EMT-related genes in the prognostic prediction of Wilms tumor.","authors":"Kexin Meng, Zerui Zhao, Yaqing Gao, Keliang Wu, Wei Liu, Xiaoqing Wang, Yi Zheng, Wei Zhao, Bei Wang","doi":"10.3389/fmolb.2024.1469775","DOIUrl":"10.3389/fmolb.2024.1469775","url":null,"abstract":"<p><p>Wilms tumor (WT) is the most common type of malignant abdominal tumor in children; it exhibits a high degree of malignancy, grow rapidly, and is prone to metastasis. This study aimed to construct a prognosis model based on anoikis-related genes (ARGs) and epithelial-mesenchymal transition (EMT)-related genes (ERGs) for WT patients; we assessed the characteristics of the tumor microenvironment and treatment efficacy, as well as identifying potential therapeutic targets. To this end, we downloaded transcriptome sequencing data and clinical data for WT and normal renal cortices and used R to construct and validate the prognostic model based on ARGs and ERGs. Additionally, we performed clinical feature analysis, nomogram construction, mutation analysis, drug sensitivity analysis, Connectivity Map (cMAP) analysis, functional enrichment analysis, and immune infiltration analysis. Finally, we screened the hub gene using the STRING database and validated it via experiments. In this way, we constructed a model with good accuracy and robustness, which was composed of seven anoikis- and EMT-related genes. Paclitaxel and mesna were selected as potential chemotherapeutic drugs and adjuvant chemotherapeutic drugs for the WT high-risk group by using the Genomics of Drug Sensitivity in Cancer (GDSC) and cMAP compound libraries, respectively. We proved the existence of a strong correlation between invasive immune cells and prognostic genes and risk scores. Next, we selected NTRK2 as the hub gene, and <i>in vitro</i> experiments confirmed that its inhibition can significantly inhibit the proliferation and migration of tumor cells and promote late apoptosis. In summary, we screened out the potential biomarkers and chemotherapeutic drugs that can improve the prognosis of patients with WT.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344656","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}