Article(id=1203053369242906950, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203053366290113441, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2023.03.0267, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1642521600000, receivedDateStr=2022-01-19, revisedDate=null, revisedDateStr=null, acceptedDate=1650038400000, acceptedDateStr=2022-04-16, onlineDate=1764759874878, onlineDateStr=2025-12-03, pubDate=1679932800000, pubDateStr=2023-03-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1764759874878, onlineIssueDateStr=2025-12-03, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1764759874878, creator=13701087609, updateTime=1764759874878, updator=13701087609, issue=Issue{id=1203053366290113441, tenantId=1146029695717560320, journalId=1189873630562394117, year='2023', volume='48', issue='3', pageStart='245', pageEnd='366', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1764759874174, creator=13701087609, updateTime=1764810242575, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1203264626747220064, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203053366290113441, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1203264626747220065, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203053366290113441, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=267, endPage=274, ext={EN=ArticleExt(id=1203053369540702547, articleId=1203053369242906950, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Effect of CUL3 on proliferation, migration and invasion of gastric cancer cells and its mechanism, columnId=1190310110212751762, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Basic Research, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the effect and its mechnism of ubiquitin ligase cullin3 (CUL3) on the proliferation, migration and invasion of gastric cancer cells. Methods The expression of CUL3 in gastric cancer and adjacent tissues and its relationship with clinical prognosis were analyzed based on TCGA database. HGC-27 and BGC-823 cells were transfected with CUL3 shRNA and empty lentivirus to construct a CUL3 knockdown gastric cancer cell line group (shCUL3 group) and an empty lentivirus transfection group (Vector group). CCK-8 assay, clone formation assay, EdU staining, scratch assay and Transwell assay were used to detect the changes of proliferation, migration and invasion ability of the two groups; Western blotting was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins and PI3K/Akt/GSK3β pathway proteins in two groups;The changes of migration and invasion ability of shCUL3 group were detected after application of PI3K agonist 740 Y-P. Results In the TCGA database, CUL3 was highly expressed in gastric cancer, and was significantly associated with poor prognosis of gastric cancer patients. Compared with Vector group, CCK-8, clone formation assay and EdU staining showed that the proliferation of gastric cancer cells in shCUL3 group was inhibited (P<0.05), and CUL3 shRNA could significantly inhibit cell migration and invasion (P<0.05); In addition, compared with Vector group, the expression of E-cadherin protein in shCUL3 group increased, and the protein levels of vimentin, β-catenin, p-PI3K, p-Akt and p-GSK-3β significantly decreased (P<0.05); In contrast, application of the PI3K agonist 740 Y-P could partially reverse the inhibitory effect of CUL3 shRNA on gastric cancer cell migration and invasion. Conclusions Knockdown of CUL3 can inhibit the proliferation, migration and invasion of gastric cancer cells, and the mechanism of action of CUL3 in gastric cancer may be related to the activation of PI3K/Akt/GSK3β signaling pathway.

, correspAuthors=Hua-Ping Xie, 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=Min Liu, Yun-Lian Hu, Hua-Ping Xie), CN=ArticleExt(id=1203053371532996983, articleId=1203053369242906950, tenantId=1146029695717560320, journalId=1189873630562394117, language=CN, title=CUL3对胃癌细胞增殖、迁移和侵袭的作用及其机制, columnId=1190310110472798614, journalTitle=解放军医学杂志, columnName=基础研究, runingTitle=null, highlight=null, articleAbstract=

目的 探讨泛素连接酶Cullin3（CUL3）对胃癌细胞增殖、迁移和侵袭能力的影响及其作用机制。方法 基于TCGA数据库分析CUL3在胃癌和癌旁组织中的表达及其与临床预后的关系。采用CUL3 shRNA和空载慢病毒转染HGC-27和BGC-823细胞，构建CUL3敲低胃癌细胞系组（shCUL3组）与空载慢病毒转染组（空载组）。采用CCK-8法、克隆形成实验、EdU染色、划痕实验和Transwell实验检测两组的增殖、迁移和侵袭能力；采用Western blotting检测两组上皮-间质转化（EMT）相关蛋白和PI3K/Akt/GSK3β通路蛋白的表达情况；应用PI3K激动剂740 Y-P后检测shCUL3组细胞迁移和侵袭能力的变化。结果 TCGA数据库中CUL3在胃癌中呈高表达，且与胃癌患者预后不良明显相关。CCK-8、克隆形成实验和EdU染色结果显示，与空载组比较，shCUL3组胃癌细胞增殖能力受到抑制（P<0.05），且CUL3 shRNA可明显抑制细胞的迁移和侵袭能力（P<0.05）。与空载组比较，shCUL3组E-cadherin蛋白表达升高，波形蛋白、β-catenin、p-PI3K、p-Akt及p-GSK-3β蛋白表达明显降低（P<0.05）。与shCUL3组比较，应用PI3K激动剂740 Y-P可部分逆转CUL3 shRNA对胃癌细胞迁移和侵袭的抑制作用。结论 敲低CUL3可抑制胃癌细胞的增殖、迁移和侵袭过程，CUL3在胃癌中的作用机制可能与激活PI3K/Akt/GSK3β信号通路相关。

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刘敏，硕士研究生，副主任医师，主要从事消化道肿瘤的基础与临床研究

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刘敏，硕士研究生，副主任医师，主要从事消化道肿瘤的基础与临床研究

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Chin J Nat Med, 2016, 14(1):48-55., articleTitle=Baicalin attenuates high fat diet-induced insulin resistance and ectopic fat storage in skeletal muscle, through modulating the protein kinase B/Glycogen synthase kinase 3 beta pathway, refAbstract=null)], funds=[Fund(id=1203053376486470276, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, awardId=2017KFYXJ114, language=EN, fundingSource=Independent Innovation Research Fund of Huazhong University of Science and Technology(2017KFYXJ114), fundOrder=null, country=null), Fund(id=1203053376582939274, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, awardId=2017KFYXJ114, language=CN, fundingSource=华中科技大学自主创新研究基金(2017KFYXJ114), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1203053371797238153, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, xref=1, ext=[AuthorCompanyExt(id=1203053371805626762, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, companyId=1203053371797238153, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=¹Department of Gastroenterology, the People's Hospital of Sanya, Sanya, Hainan 572000, China), AuthorCompanyExt(id=1203053371809821067, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, companyId=1203053371797238153, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=¹海南省三亚市人民医院消化内科，海南三亚 572000)]), AuthorCompany(id=1203053371893707152, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, xref=2, ext=[AuthorCompanyExt(id=1203053371906290065, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, companyId=1203053371893707152, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=²Department of Spleen and Stomach, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430061, China), AuthorCompanyExt(id=1203053371914678674, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, companyId=1203053371893707152, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=²湖北省中医医院脾胃科，湖北武汉 430061)]), AuthorCompany(id=1203053372061479320, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, xref=3, ext=[AuthorCompanyExt(id=1203053372069867929, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, companyId=1203053372061479320, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=³Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China), AuthorCompanyExt(id=1203053372078256539, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, companyId=1203053372061479320, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=³华中科技大学同济医学院附属同济医院消化内科，湖北武汉 430030)])], figs=[ArticleFig(id=1203053375584694854, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, language=EN, label=Fig. 1, caption=Expression level of CUL3 in gastric cancer, figureFileSmall=ieLijpAMU1AKaQ7hXP2Flw==, figureFileBig=63iRomlCe9nasYb7abwN4Q==, tableContent=null), ArticleFig(id=1203053375693746766, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, language=CN, label=图1, caption=CUL3在胃癌中的表达水平

T. 胃癌组织；N. 癌旁组织；A. CUL3在全身不同肿瘤中的表达情况；B. CUL3在正常组织与胃癌组织中的表达；C. CUL3在胃癌不同分期中的表达情况；D. CUL3在胃癌不同分级的表达情况；E. CUL3与胃癌患者预后的关系；F. Western blotting检测CUL3在胃癌组织和癌旁组织中的表达；G. Western blotting检测CUL3在正常胃黏膜上皮细胞和4种胃癌细胞系中的表达情况；*P<0.05，**P<0.01，***P<0.001

, figureFileSmall=ieLijpAMU1AKaQ7hXP2Flw==, figureFileBig=63iRomlCe9nasYb7abwN4Q==, tableContent=null), ArticleFig(id=1203053375920239193, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, language=EN, label=Fig. 2, caption=Effect of knockdown of CUL3 on the proliferation of gastric cancer cells, figureFileSmall=3GxuCkKKxx29OPA8vf1hlA==, figureFileBig=qDGN3EyU3udzy8zdT0esGw==, tableContent=null), ArticleFig(id=1203053376004125281, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, language=CN, label=图2, caption=敲低CUL3对胃癌细胞增殖的影响

A. 倒置荧光显微镜下的细胞转染情况(×100)；B. Western blotting检测CUL3蛋白的敲低情况；C. CCK-8法检测敲低CUL3对胃癌细胞活力的影响，**P<0.01；D. 克隆形成实验检测敲低CUL3对细胞克隆形成能力的影响；E. EdU检测敲低CUL3对细胞增殖的影响(EdU+DAPI染色，×400)

, figureFileSmall=3GxuCkKKxx29OPA8vf1hlA==, figureFileBig=qDGN3EyU3udzy8zdT0esGw==, tableContent=null), ArticleFig(id=1203053376108982887, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, language=EN, label=Fig. 3, caption=Effect of knockdown of CUL3 on migration and invasion of gastric cancer cells, figureFileSmall=YcEJBUr6LryV5xU3gSK8AA==, figureFileBig=4iQjzpM38CziOCcTH1ZH1A==, tableContent=null), ArticleFig(id=1203053376171897454, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, language=CN, label=图3, caption=敲低CUL3对胃癌细胞迁移和侵袭的影响

EMT. 上皮-间质转化；A. 细胞划痕实验检测敲低CUL3对胃癌细胞迁移能力的影响；B. Transwell实验检测敲低CUL3对胃癌细胞侵袭能力的影响(0.1%结晶紫染色×200)；C. Western blotting检测EMT相关蛋白表达的变化

, figureFileSmall=YcEJBUr6LryV5xU3gSK8AA==, figureFileBig=4iQjzpM38CziOCcTH1ZH1A==, tableContent=null), ArticleFig(id=1203053376268366453, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, language=EN, label=Fig. 4, caption=Effect of knockdown of CUL3 on PI3K/Akt/GSK3β pathway, figureFileSmall=9jqtYAFB22AZilztfs3PZQ==, figureFileBig=uE7y7kbV4mAOgSI/aAL6MA==, tableContent=null), ArticleFig(id=1203053376352252539, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203053369242906950, language=CN, label=图4, caption=敲低CUL3对PI3K/Akt/GSK3β通路的影响

A. Western blotting检测PI3K/Akt/GSK3β通路蛋白的表达变化；B、C. 740 Y-P对CUL3敲低胃癌细胞迁移能力的影响(×40)；D. 740 Y-P对CUL3敲低胃癌细胞侵袭能力的影响(0.1%结晶紫染色×200)

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