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A combined workflow evaluates 6-gingerol effects on DNMTs using bioinformatics protein structure prediction, docking, molecular dynamics, and ADMET profiling, together with experimental measurement of miRNA and PODXL expression. Results show 6-gingerol alters miRNA levels, lowering DNMT1 and DNMT3A in NB4 cells, which in turn affects PODXL expression and oncogenic phenotypes. Treatment also increases miR-193a and miR-200c, contributing to dysregulation of tumor suppressor genes, including reduced PODXL.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/6-gingerol-modulates-mirnas-and-podxl-gene-expression-via-methyltransferase-enzymes-in-nb4-cells-an-in-silico-and-in-vitro-study/331092/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/6-gingerol-modulates-mirnas-and-podxl-gene-expression-via-methyltransferase-enzymes-in-nb4-cells-an-in-silico-and-in-vitro-study/331092.png","ImageObject",300,407,{"name":92,"@type":93},"Oliver","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main focus of the study in NB4 cells?","Question",{"text":112,"@type":113},"The study examines how predicted microRNAs regulate DNA methyltransferases (DNMTs) and the PODXL gene in NB4 cells in the context of AML pathogenesis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which computational methods are used to study 6-gingerol’s potential effects on DNMTs?",{"text":117,"@type":113},"Protein structure prediction, docking, molecular dynamics, and ADMET profiling are included as part of the bioinformatics framework.",{"name":119,"@type":110,"acceptedAnswer":120},"What gene and miRNA changes occur after 6-gingerol treatment?",{"text":121,"@type":113},"Post-treatment, DNMT1 and DNMT3A expression changes are observed, along with upregulation of miR-193a and miR-200c, which relates to altered PODXL expression and cancer-related traits.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},331092,1791001251,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},8796095461610,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \n6‑Gingerol modulates miRNAsand PODXL gene expression via methyltransferase enzymes in NB4 cells: an in silico and in vitro study  \nAli Afgar1, Mahdiyeh RamezaniZadeh Kermani2, Athareh Pabarja3, Amir Reza Afgar1, Batoul Kavyani4, Hossein Arezoomand5, Saeed Zanganeh6, Mohammad Javad Sanaei7, Mahla Sattarzadeh Bardsiri6,8* & RezaVahidi1*  \nThis investigation delves into the influence of predicted microRNAs on DNA methyltransferases (DNMTs) and the PODXL gene within the NB4 cell line, aiming to elucidate their roles in the pathogenesis of acute myeloid leukemia (AML). A comprehensive methodological framework was adopted to explore the therapeutic implications of 6‑gingerol on DNMTs. This encompassed a suite of bioinformatics tools for protein structure prediction, docking, molecular dynamics, and ADMET profiling, alongside empirical assessments of miRNA and PODXL expression levels. Such a multifaceted strategy facilitated an in‑depth understanding of 6‑gingerol’s potential efficacy in DNMT modulation. The findings indicate a nuanced interplay where 6‑gingerol administration modulated miRNA expression levels, decreasing in DNMT1 and DNMT3A expression in NB4 cells. This alteration indirectly influenced PODXL expression, contributing to the manifestation of oncogenic phenotypes. The overexpression of DNMT1 and DNMT3A in NB4 cells may contribute toAML, which appears modulable via microRNAs such as miR‑193a and miR‑200c. Post‑treatment with 6‑gingerol, DNMT1 and DNMT3A expression alterations were observed, culminating in the upregulation of miR‑193a  \nand miR‑200c. This cascade effect led to the dysregulation of tumor suppressor genes in cancer cells, including downregulation of PODXL, and the emergence of cancerous traits. These insights underscore the therapeutic promise of 6‑gingerol in targeting DNMTs and microRNAs within theAML context.  \nKeywords PODXL gene, Methyltransferase, NB4 cell line, AML, MiRNA, Molecular dynamic simulation, Docking  \nAcute myeloid leukemia (AML) is a malignant disease, known for its diversity of phenotype and genetics, with the highest mortality rate among hematopoietic neoplasms. It is characterized by the clonal transformation of myeloid precursors with lower differentiation abilities. It has been demonstrated that 4 out 5 of AML patients are adults1. Acute promyelocytic leukemia (APL) accounted for one in ten cases ofAML. It usually affects younger individuals compared to other subtypes ofAML2. APL is mainly distinguished by a chromosome translocation t (15; 17) (q24; q21), which is involved in the PML/RARA gene fusion. Retinoids are implicated in the activation of retinoic acid receptors (RARs α, β, and γ), and retinoid X receptors (RXRs). RARα is capable of interacting with RXR, and the RARα-RXR heterodimer can manage the corepressor or coactivator involved in the regulation of  \n1Research Center for Hydatid Diseases in Iran, Kerman University of Medical Sciences, Kerman, Iran. 2Department of Mathematics, Shahid Bahonar University of Kerman, Kerman, Iran. 3Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran. 4Department of Medical Microbiology (Bacteriology & Virology), Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran. 5Department of Hematology and Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran. 6Stem Cells and Regenerative Medicine Innovation Center, Kerman University of Medical Sciences, Kerman, Iran. 7School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 8Student Research Committee, Faculty of Allied Medicine, Kerman University of Medical  \nSciences, Kerman, Iran.* email: [sabasatarzadeh3261@gmail.com](sabasatarzadeh3261@gmail.com); [reza.vahidi2009@gmail.com](reza.vahidi2009@gmail.com)  \n[www. nature.com/scientificreports/](www. nature","cbCaiuCrEyh4csVK","https://ap.wps.com/l/cbCaiuCrEyh4csVK","pdf",1983173,17,"English","# Background\n## Acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL)\n## Epigenetic regulation by DNMTs and DNA methylation\n## miRNAs as regulators of DNMT expression\n## Role of PODXL in cancer","[{\"question\":\"What is the main focus of the study in NB4 cells?\",\"answer\":\"The study examines how predicted microRNAs regulate DNA methyltransferases (DNMTs) and the PODXL gene in NB4 cells in the context of AML pathogenesis.\"},{\"question\":\"Which computational methods are used to study 6-gingerol’s potential effects on DNMTs?\",\"answer\":\"Protein structure prediction, docking, molecular dynamics, and ADMET profiling are included as part of the bioinformatics framework.\"},{\"question\":\"What gene and miRNA changes occur after 6-gingerol treatment?\",\"answer\":\"Post-treatment, DNMT1 and DNMT3A expression changes are observed, along with upregulation of miR-193a and miR-200c, which relates to altered PODXL expression and cancer-related traits.\"}]","6-Gingerol modulates miRNAs and PODXL gene expression via methyltransferase enzymes in NB4 cells: an in silico and in vitro study | PDF",1789991763,43]