Cell cycle dysregulation with overexpression of KIF2C/MCAK is a critical event in
作者机构：Department of OtolaryngologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing Medical UniversityChongqing 400016China Department of Biochemistry and Molecular BiologyChongqing Medical UniversityChongqing 400016China Molecular Medicine and Cancer Research CenterChongqing Medical UniversityChongqing 400016China
出 版 物：《Genes & Diseases》 (基因与疾病（英文）)
年 卷 期：2023年第10卷第1期
页 面：212-227页
核心收录：
学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 0703[理学-化学] 10[医学]
基 金：This research was funded by the National Natural Science Foundation of China(No.81902824) The First Affiliated Hospital of Chongqing Medical University,Chongqing,China.
主 题：Bioinformatics Cell cycle KIF2C Mitosis Nasopharyngeal carcinoma
摘 要：Nasopharyngeal carcinoma(NPC)is a common malignant carcinoma of the head and neck,and the biological mechanisms underlying the pathogenesis of NPC remain not fully understood.In the present study,we systematically analyzed four independent NPC transcriptomic datasets and focused on identifying the critical molecular networks and novel key hub genes implicated in NPC.We found totally 170 common overlapping differentially expressed genes(DEGs)in the four NPC datasets.GO and KEGG pathway analysis revealed that cell cycle dysregulation is a critical event in NPC.Protein-protein interaction(PPl)network analysis identified a 15 hub-gene corenetwork with overexpressedkinesin family member2C(KIF2C)as a central regulator.Loss-of-function study demonstrated that knockdown of KiF2C significantly inhibited cell growth and cell motility,and delayed cell cycle progression,accompanied with dramatic mitotic defects in spindle formation in NPC cells.RNA-seq analysis revealed that KIF2c knockdown led to deregulation of various downstream genes.KiF2C could also regulate the AKT/mTOR pathways,and enhance paclitaxel sensitivity in NPC cells.Taken together,our results suggest that cell cycle dysregulation is a critical event during NPC pathogenesis and KIF2C is a novel key mitotic hub gene with therapeutic potential in NPC.
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