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This study evaluates how the circular RNA circEPHB4 regulates glioma malignant behaviors through molecular interactions involving YBX1 and MRPS16. Methods combine EdU and CCK-8 for proliferation, Transwell for invasion and migration, xenografts with bioluminescence imaging, and expression detection by qRT-PCR, RNA FISH, IHC, or western blot. Mechanistic assays include RIP and RNA pull-down, plus co-IP and ubiquitination analyses. Results show circEPHB4 knockdown or MRPS16 inhibition suppresses glioma progression, revealing YBX1-mediated m5C modification to stabilize MRPS16 and RBBP6-related ubiquitin-proteasome control of YBX1.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/circephb4-binds-toybx1-to-upregulate-mrps16-and-promotes-glioma-progression/450382/",{"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/circephb4-binds-toybx1-to-upregulate-mrps16-and-promotes-glioma-progression/450382.png","ImageObject",300,407,{"name":92,"@type":93},"Rhys","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-04","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main finding about circEPHB4 in glioma progression?","Question",{"text":112,"@type":113},"CircEPHB4 promotes glioma proliferation, migration, and invasion by increasing MRPS16 expression and enhancing glioma growth both in vitro and in vivo.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does circEPHB4 affect MRPS16 at the post-transcriptional level?",{"text":117,"@type":113},"CircEPHB4 enhances MRPS16 mRNA stability through YBX1-mediated m5C modification.",{"name":119,"@type":110,"acceptedAnswer":120},"How is YBX1 degradation regulated and what role does RBBP6 play?",{"text":121,"@type":113},"RBBP6 catalyzes YBX1 ubiquitination; circEPHB4 competes with RBBP6 to bind YBX1 and inhibit ubiquitin-proteasomal degradation of YBX1.","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},450382,1790820194,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Cellular and Molecular Life Sciences (2026) 83:32  \n[https://doi.org/10.1007/s00018-025-06002-2](https://doi.org/10.1007/s00018-025-06002-2) Cellular and Molecular Life Sciences  \nORIGINAL ARTICLE  \nCircEPHB4 binds toYBX1 to upregulate MRPS16 and promotes glioma progression  \nYuxiang Liao1,2 · Bo Liu1 · Zhiping Zhang1 · Qian Zhang1 · Mingyong Xiang1 · Chen Jin1,2  \nReceived: 1 September 2025 / Revised: 18 November 2025 / Accepted: 22 November 2025 © The Author(s) 2025  \nAbstract  \nBackground Glioma is the most frequently diagnosed brain tumor in adults worldwide which is associated with unfavorable prognosis and survival time. However, the understanding of glioma progression remains limited.  \nMethods The cell proliferation in glioma cells were monitored by EdU incorporation and CCK-8 assays. Glioma cell invasion and migration were assessed by Transwell assay. In vivo tumorigenesis were detected by xenograft study with bioluminescence imaging. qRT-PCR, RNA FISH, IHC or western blot were used to detect circEPHB4, MRPS16, YBX1, RBBP6 and other molecules expression. The associations between YBX1 and MRPS16 mRNA, as well as between circEPHB4 and YBX1, were detected by RNA immunoprecipitation (RIP) and RNA pull-down assays. In addition, the ubiquitination of YBX1 and RBBP6-YBX1 interaction were assessed by co-immunoprecipitation (co-IP) .  \nResults Knockdown of circEPHB4 or MRPS16 inhibited glioma progression in vitro and in vivo. circEPHB4 promoted glioma cell proliferation, migration, and invasion via increasing MRPS16 expression in vitro. At the post-transcriptional level, circEPHB4 enhanced MRPS16 mRNA stability through YBX1-mediated m5C modification in vitro. At the post-translational level, RBBP6 catalyzed the ubiquitination of YBX1, and circEPHB4 competed with RBBP6 to bind YBX1 to inhibit the ubiquitin-proteasomal degradation of YBX1 in vitro. circEPHB4 interacted with YBX1 to promote glioma cell growth via inducing MRPS16 in vitro and in vivo.  \nConclusion circEPHB4 bound toYBX1 to inhibit RBBP6-mediated degradation and increase its expression, thus enhancing MRPS16 mRNA stability via m5C modification, and ultimately promoting glioma progression.  \nKeywords circEPHB4 · MRPS16 · YBX1 · RBBP6 · Glioma  \nAbbreviations  \nAAV adeno-associated virus  \nCHX cycloheximide  \nco-IP co-immunoprecipitation  \nCQ chloroquine  \nEPHB4 Ephrin receptor B4  \nESCC esophageal squamous cell carcinoma FISH fluorescence in situ hybridization  \n􀀍 Chen Jin [jinchen@csu.edu.cn](jinchen@csu.edu.cn)  \n1 Department of Neurosurgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, Hunan Province 410008, P.R. China  \n2 National Clinical Research Center for Geriatric Disorders (XiangYa Hospital), No. 87, Xiangya Road, Changsha, Hunan Province 410008, P.R. China  \nIF  \nIHC  \nLAUD  \nm5CMRPS16 mt-LSU  \nmt-SSUncRNAs PFA  \nRBBP6  \nRBPs  \nRIP  \nrRNA  \ntRNA  \nYBX1  \nimmunofluorescence immunohistochemistry lung adenocarcinoma 5-methylcytosine  \nmitochondrial ribosomal protein S16  \nmitochondrial large ribosomal subunit  \nmitochondrial small ribosomal subunit non-coding RNAs paraformaldehyde  \nretinoblastoma-binding protein 6 RNA binding proteins  \nRNA immunoprecipitation ribosomal RNA  \ntransfer RNA  \nY-box binding protein 1  \n1 3  \nIntroduction  \nGlioma is the most frequently diagnosed brain tumor in adults worldwide, and it accounts for approximately 30% of primary brain tumors [1] . Despite the advances in surgery, radio-and chemotherapies, the survival time and prognosis of most patients with glioma remain unfavorable [2] . The median survival of high-grade glioma is ~ 15–36 month [3] . Even after surgical resection, the residual glioma cells contribute to local recurrence and metastasis of glioma [4] . It is of clinical significance to desipher the mechanisms underlying glioma tumor progression.  \nIn recent years, non-coding RNAs have emerged as crucial regulators in glioma pathogenesis. Among these, circular RNAs (circRNAs) represe","cbCaifsoVyVJRd8Y","https://ap.wps.com/l/cbCaifsoVyVJRd8Y","pdf",21379255,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Keywords\n# Abbreviations\n# Introduction","[{\"question\":\"What is the main finding about circEPHB4 in glioma progression?\",\"answer\":\"CircEPHB4 promotes glioma proliferation, migration, and invasion by increasing MRPS16 expression and enhancing glioma growth both in vitro and in vivo.\"},{\"question\":\"How does circEPHB4 affect MRPS16 at the post-transcriptional level?\",\"answer\":\"CircEPHB4 enhances MRPS16 mRNA stability through YBX1-mediated m5C modification.\"},{\"question\":\"How is YBX1 degradation regulated and what role does RBBP6 play?\",\"answer\":\"RBBP6 catalyzes YBX1 ubiquitination; circEPHB4 competes with RBBP6 to bind YBX1 and inhibit ubiquitin-proteasomal degradation of YBX1.\"}]","CircEPHB4 binds toYBX1 to upregulate MRPS16 and promotes glioma progression | PDF",1790733033,48]