靶向敲除CDK2致人黑素瘤移植瘤的蛋白质组改变  

Proteomic Alterations in Xenograft of Human Melanoma by Targeting Knockout of Cyclin-Dependent Kinase 2

作　　者：刘厚广[1] 李铮 霍珊珊 魏琼玲 张海梅 吴剑宾 蒋雅雯 LIU Hou-Guang;LI Zheng;HUO Shan-Shan;WEI Qiong-Ling;ZHANG Hai-Mei;WU Jian-Bin;JIANG Ya-Wen(Department of Dermatology,the Third Hospital of Xiamen,Xiamen 361100,China)

机构地区：[1]厦门市第三医院皮肤科,厦门361100

出　　处：《应用化学》2025年第3期345-352,共8页Chinese Journal of Applied Chemistry

基　　金：福建省卫生健康科技计划项目-省医学创新课题(No.2021CXB027)资助。

摘　　要：人黑色素瘤具有较高的发病率和死亡率,特别是高级别的恶性黑色素瘤严重威胁着人类健康。人黑色素瘤细胞的细胞周期失去调控是黑色素瘤生成的先决条件,其中细胞周期蛋白依赖性激酶2(CDK2)在细胞周期调控中具有重要作用。然而,CDK2如何调控人黑色素瘤细胞的蛋白质组目前仍是未知。本文研究了靶向敲除CDK2对人黑色素瘤移植瘤蛋白质组的影响。结果表明,重组sgCDK2-108慢病毒感染人黑色素瘤细胞A375的小鼠移植瘤后,与肿瘤组相比,CDK2靶向敲除组共有185个DEPs(下调68个DEPs、上调117个DEPs)发生显著改变;与CDK2靶向敲除阴性对照组相比,CDK2靶向敲除组共有203个DEPs(下调98个DEPs、上调105个DEPs)发生显著改变。Rps29、Adrm1、Fam162a和Rps15为靶向敲除CDK2后共同下调的DEPs,Obp1b、Serpinb1a、Ttr和Slc9a3r1为靶向敲除CDK2后共同上调的DEPs。DEPs主要参与肽酶活性调节、肽链内切酶活性调节及水解酶活性负调节等生物学过程。本研究揭示了CDK2在人黑色素瘤生成过程中的调控网络和生物功能的作用,为靶向CDK2治疗人黑色素瘤提供新的参考。Human melanoma is a cutaneous melanoma with high morbidity and mortality,especially for advanced malignant melanoma which pose a seriously threat to human health.Dysregulation of cell cycle of human melanoma cell is sufficient to cause human melanoma.Among the cyclin-dependent kinases(CDKs),CDK2 plays an important role in regulation of cell cycle.However,how CDK2 regulate the proteome of human melanoma cell remains unknown.In this study,the proteomic alterations in human melanoma xenograft by targeting knockout of CDK2 were studied.The results showed that a total of 185 differentially expressed proteins(DEPs)were identified as significantly changed DEPs,68 DEPs were down-regulated and 117 DEPs were up-regulated in CDK2 knockout(CDK2-KO)group compared with tumor group.A total of 203 DEPs were identified as significantly changed DEPs,98 DEPs were down-regulated and 105 DEPs were up-regulated in CDK2-KO group compared with CDK2 knockout negative(CDK2-NC)group after human melanoma xenograft was infected with recombinant sgCDK2-108 lentivirus.Rps29,Adrm1,Fam162a and Rps15 were same down-regulated DEPs,Obp1b,Serpinb1a,Ttr and Slc9a3r1 were same up-regulated DEPs.These DEPs mainly referred to biological processes such as regulation of peptidase activity,regulation of endopeptidase activity,negative regulation of hydrolase activity.This study reveals the role of CDK2 in regulation network and biological function in human melanoma and provides a novel evidence for targeting CDK2 in human melanoma therapy.

关 键 词：人黑色素瘤 CDK2 蛋白质组 移植瘤 

分 类 号：O654.9[理学—分析化学]