Article(id=1198558269552820554, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1198558265329152414, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.1335.2024.0408, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1696867200000, receivedDateStr=2023-10-10, revisedDate=null, revisedDateStr=null, acceptedDate=1702656000000, acceptedDateStr=2023-12-16, onlineDate=1763688159596, onlineDateStr=2025-11-21, pubDate=1722096000000, pubDateStr=2024-07-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1763688159596, onlineIssueDateStr=2025-11-21, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1763688159596, creator=13701087609, updateTime=1763688159596, updator=13701087609, issue=Issue{id=1198558265329152414, tenantId=1146029695717560320, journalId=1189873630562394117, year='2024', volume='49', issue='7', pageStart='733', pageEnd='854', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1763688158589, creator=13701087609, updateTime=1763689196450, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1198562618517581944, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1198558265329152414, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1198562618517581945, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1198558265329152414, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=832, endPage=840, ext={EN=ArticleExt(id=1198558269812867417, articleId=1198558269552820554, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Role and mechanism of WDR82 in the genesis and development of glioma, columnId=1190310110212751762, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Basic Research, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the role and underlying mechanisms of WD repeat domain 82 (WDR82) protein in the pathogenesis and progression of glioma. Methods We analyzed the expression level of WDR82 in glioma tissues using GEPIA and UALCAN databases and further assessed WDR82 protein expression in glioma and adjacent normal tissues through immunohistochemical staining. The correlation between WDR82 expression and the prognosis of glioma patient was evaluated using Kaplan-Meier plotter. Experiments were conducted on A172 and U251 cell lines, which were categorized into four groups: control group (transfected with 3 μg pcDNA3), shR-control group (transfected with 3 μg pSilencer 2.1-U6), pWDR82 group (transfected with 3 μg pWDR82), and shR-WDR82 group (transfected with 3 μg shR-WDR82). Post-transfection, we confirmed transfection efficiency at 48 hours using qRT-PCR and measured cell viability at the same time point with CCK-8 assay. Clone formation assay was employed to assess cell proliferation capacity after 14 days of transfection, while flow cytometry was utilized to analyze cell apoptosis after 48 hours of transfection. Additionally, Western blotting was conducted to determine the expression levels of proteins related to proliferation and Akt/mTOR signaling pathway after 48 hours of transfection. Finally, the effect of WDR82 on tumor growth in NOD-SCID mice was investigated using tumor carrying experiment in vivo. Results Analysis of WDR82 expression in glioma tissues using GEPIA and UALCAN databases, along with immunohistochemical staining, revealed significantly higher expression levels compared to normal and paracancerous tissues (P<0.05). Additionally, WDR82 expression was not associated with gender or age of patients (P>0.05). Kaplan-Meier plotter analysis indicated that elevated WDR82 expression correlated with a poor prognosis in glioma patients (log-rank P=0.029). Overexpression of WDR82 notably enhanced the proliferation and inhibited the apoptosis of A172 and U251 cells, and also significantly upregulated the expression of MKI67, BCL2, CCND1, p-Akt and p-mTOR in A172 and U251 cells (P<0.05). Conversely, WDR82 knockdown had the opposite effects, inhibiting cell proliferation, increasing apoptosis and downregulating the expression of MKI67, BCL2, CCND1, p-Akt and p-mTOR (P<0.05). WDR82 knockdown in U251 cells significantly inhibited tumor growth in NOD-SCID mice (P<0.05). Conclusion High expression of WDR82 promotes the proliferation of glioma cells and the growth of tumors in vivo by regulating the AKT/mTOR signaling pathway.

, correspAuthors=Zhen Yang, authorNote=null, correspAuthorsNote=, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Yun Gao, Jun-Miao Ge, Xuan Wang, Zhen Yang), CN=ArticleExt(id=1198558271469617594, articleId=1198558269552820554, tenantId=1146029695717560320, journalId=1189873630562394117, language=CN, title=WDR82在神经胶质瘤发生发展中的作用及其机制, columnId=1190310110472798614, journalTitle=解放军医学杂志, columnName=基础研究, runingTitle=null, highlight=null, articleAbstract=

目的 探讨WD重复结构域82(WDR82)蛋白在神经胶质瘤发生发展中的作用及其机制。方法 利用GEPIA和UALCAN数据库分析WDR82在神经胶质瘤组织中的表达情况；采用Kaplan-Meier生存分析WDR82表达与神经胶质瘤患者预后的关系。采用组织芯片进行免疫组织化学染色检测WDR82在神经胶质瘤组织及其癌旁组织中的表达情况。取人胶质瘤A172和U251细胞，设置对照组(转染3 μg pcDNA3)、pWDR82组(转染3 μg pWDR82)、shR-Con组(转染3 μg pSilencer 2.1-U6)、shR-WDR82组(转染3 μg shR-WDR82)。转染48 h后，采用qRT-PCR验证各组转染效率；CCK-8法检测转染48 h的细胞活性，克隆形成实验检测转染后14 d的细胞增殖能力，流式细胞术检测转染48 h的细胞凋亡情况；Western blotting检测转染48 h细胞中增殖相关蛋白及Akt/mTOR信号通路相关蛋白的表达。采用体内荷瘤实验检测WDR82对NOD-SCID小鼠肿瘤生长的影响。结果 GEPIA和UALCAN数据库分析及免疫组织化学染色结果显示，WDR82在神经胶质瘤组织中的表达水平明显高于癌旁正常组织(P<0.05)，其表达在不同性别及年龄段患者间差异无统计学意义(P>0.05)。Kaplan-Meier生存分析结果显示，高表达WDR82的神经胶质瘤患者的预后不良(log-rank P=0.029)。过表达WDR82可明显促进A172和U251细胞的增殖，抑制细胞凋亡，明显增高A172和U251细胞中MKI67、BCL2、CCND1、p-Akt和p-mTOR的表达(P<0.05)。反之，敲降WDR82则抑制A172和U251细胞的增殖，促进细胞凋亡，降低MKI67、BCL2、CCND1、p-Akt和p-mTOR的表达(P<0.05)。敲降U251细胞中的WDR82，可明显抑制荷瘤NOD-SCID小鼠肿瘤的生长(P<0.05)。结论 高表达WDR82可能通过调控Akt/mTOR信号通路促进神经胶质瘤细胞的增殖及体内肿瘤的生长。

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WDR82. WD重复结构域82基因；A. UALCAN数据库分析正常组织和神经胶质瘤组织中WDR82蛋白相对表达水平；B. GEPIA数据库分析正常组织和神经胶质瘤组织中WDR82 mRNA相对表达水平；C. UALCAN数据库分析正常组织和男性、女性神经胶质瘤患者肿瘤组织中WDR82蛋白相对表达水平；D. UALCAN数据库分析正常组织和20~40岁、41~60岁、61~80岁神经胶质瘤患者肿瘤组织中WDR82蛋白相对表达水平；E. 免疫组织化学染色检测WDR82在神经胶质瘤组织(n=57)和正常或癌旁组织(n=4)中的表达情况；F. Kaplan-Meier生存分析WDR82表达与神经胶质瘤患者预后的关系；**P<0.01，***P<0.001

, figureFileSmall=Gn6jnqZEWcE7arq97DE1jA==, figureFileBig=VnTZ2jXUeXztD/w6K+COZg==, tableContent=null), ArticleFig(id=1198589374666474040, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558269552820554, language=EN, label=Fig.2, caption=Effects of the overexpression or knockdown of WDR82 on proliferation and apoptosis of glioma cells, figureFileSmall=pxW7QSJpsm+RzdD00/5Cww==, figureFileBig=xIZawwMfd661KQ/ngJq6ow==, tableContent=null), ArticleFig(id=1198589374767137338, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558269552820554, language=CN, label=图2, caption=过表达或敲降WDR82对神经胶质瘤细胞增殖和凋亡的影响

WDR82. WD重复结构域82基因；A. qPCR检测过表达或敲降WDR82质粒的有效性；B. CCK-8法检测过表达或敲降WDR82对A172和U251细胞活性的影响；C. 克隆形成实验检测过表达或敲降WDR82对A172和U251细胞增殖能力的影响；D. 流式细胞术检测过表达或敲降WDR82对A172和U251细胞凋亡的影响；*P<0.05，**P<0.01，***P<0.001，****P<0.0001

, figureFileSmall=pxW7QSJpsm+RzdD00/5Cww==, figureFileBig=xIZawwMfd661KQ/ngJq6ow==, tableContent=null), ArticleFig(id=1198589374880383550, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558269552820554, language=EN, label=Fig.3, caption=Effect of the overexpression or knockdown of WDR82 on the expression of MKI67, BCL2, and CCND1 in glioma cells, figureFileSmall=xfrIzBqsyGUD7+XgLgjGeQ==, figureFileBig=94l/f6eiqltRvTRezt8JjA==, tableContent=null), ArticleFig(id=1198589374989435459, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558269552820554, language=CN, label=图3, caption=过表达或敲降WDR82对神经胶质瘤细胞中MKI67、BCL2和CCND1蛋白表达的影响

WDR82. WD重复结构域82基因；MKI67. 增殖标志物Ki-67；BCL2. B细胞淋巴瘤因子-2；CCND1. 细胞周期蛋白D1；A. GEPIA数据库分析神经胶质瘤组织中WDR82表达与MKI67、BCL2、CCND1表达的相关性；B. Western blotting检测过表达或敲降WDR82对A172和U251细胞中MKI67、BCL2和CCND1表达的影响；*P<0.05，**P<0.01，***P<0.001

, figureFileSmall=xfrIzBqsyGUD7+XgLgjGeQ==, figureFileBig=94l/f6eiqltRvTRezt8JjA==, tableContent=null), ArticleFig(id=1198589375115264583, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558269552820554, language=EN, label=Fig.4, caption=Effects of the overexpression or knockdown of WDR82 on Akt/mTOR signaling pathway in glioma cells, figureFileSmall=NjhrgUFvWKIQYLo/DciUSw==, figureFileBig=3zdfXBPYOXAsT6u6hy5KGg==, tableContent=null), ArticleFig(id=1198589375215927883, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558269552820554, language=CN, label=图4, caption=过表达或敲降WDR82对神经胶质瘤细胞中Akt/mTOR信号通路的影响

WDR82. WD重复结构域82；mTOR. 哺乳动物雷帕霉素靶蛋白；MYC. MYC原癌基因；SNF. U1小核糖核蛋白A基因；HIPPO. 丝氨酸/苏氨酸蛋白激酶hippo基因；Akt. 丝氨酸/苏氨酸激酶；A. UALCAN数据库分别分析对照组与mTOR信号通路异常组、MYC信号通路异常组、SNF信号通路异常组及HIPPO信号通路异常组的胶质瘤患者肿瘤组织中WDR82蛋白表达水平；B. GEPIA数据库分析神经胶质瘤组织中WDR82表达水平与mTOR和Akt1表达水平的相关性；C. Western blotting检测过表达或敲降WDR82对A172和U251细胞中p-Akt、Akt、p-mTOR、mTOR表达的影响；*P<0.05，**P<0.01，***P<0.001

, figureFileSmall=NjhrgUFvWKIQYLo/DciUSw==, figureFileBig=3zdfXBPYOXAsT6u6hy5KGg==, tableContent=null), ArticleFig(id=1198589375312396878, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558269552820554, language=EN, label=Fig.5, caption=Effect of the knockdown of WDR82 on tumor growth in tumor-bearing mice, figureFileSmall=OlOw9zCUDKGqVVj9f3tC+g==, figureFileBig=I4oHWT7oJwEj/FDx5XhnKw==, tableContent=null), ArticleFig(id=1198589375421448787, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198558269552820554, language=CN, label=图5, caption=敲降WDR82对荷瘤小鼠体内肿瘤生长的影响

WDR82. WD重复结构域82；A. 荷瘤shR-Con和shR-WDR82的U251细胞的小鼠体内肿瘤大小(n=5)；B. 荷瘤shR-Con和shR-WDR82的U251细胞的小鼠肿瘤体积生长曲线(n=5)；C. 荷瘤shR-Con和shR-WDR82的U251细胞的小鼠第25天的肿瘤重量；***P<0.001

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