Inhibition of GLUD1 mediated by LASP1 and SYVN1 contributes to hepatitis B virus X protein-induced hepatocarcinogenesis  

作　　者：Hong-Juan You Qi Li Li-Hong Ma Xing Wang Huan-Yang Zhang Yu-Xin Wang En-Si Bao Yu-Jie Zhong De-Long Kong Xiang-Ye Liu Fan-Yun Kong Kui-Yang Zheng Ren-Xian Tang 

机构地区：[1]Jiangsu Key Laboratory of Immunity and Metabolism,Department of Pathogenic Biology and Immunology,Xuzhou Medical University,Xuzhou 221004,China [2]Laboratory Department,The People’s Hospital of Funing,Yancheng 224400,China [3]National Demonstration Center for Experimental Basic Medical Sciences Education,Xuzhou Medical University,Xuzhou 221004,China

出　　处：《Journal of Molecular Cell Biology》2024年第4期31-44,共14页分子细胞生物学报（英文版）

基　　金：supported by Xuzhou Technology Bureau Foundation(KC21065);a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the Natural Science Foundation of Jiangsu Province(BK20211347);the National Natural Science Foundation of China(82372245);the Natural Science Foundation of the Jiangsu Higher Education Institutions(21KJA310004);an open Competition Grant of Xuzhou Medical University(JBGS202202).

摘　　要：Glutamate dehydrogenase 1(GLUD1)is implicated in oncogenesis.However,little is known about the relationship between GLUD1 and hepatocellular carcinoma(HCC).In the present study,we demonstrated that the expression levels of GLUD1 significantly decreased in tumors,which was relevant to the poor prognosis of HCC.Functionally,GLUD1 silencing enhanced the growth and migration of HCC cells.Mechanistically,the upregulation of interleukin-32 through AKT activation contributes to GLUD1 silencing-facilitated hepatocarcinogenesis.The interaction between GLUD1 and AKT,as well asα-ketoglutarate regulated by GLUD1,can suppress AKT activation.In addition,LIM and SH3 protein 1(LASP1)interacts with GLUD1 and induces GLUD1 degradation via the ubiquitin–proteasome pathway,which relies on the E3 ubiquitin ligase synoviolin(SYVN1),whose interaction with GLUD1 is enhanced by LASP1.In hepatitis B virus(HBV)-related HCC,the HBV X protein(HBX)can suppress GLUD1 with the participation of LASP1 and SYVN1.Collectively,our data suggest that GLUD1 silencing is significantly associated with HCC development,and LASP1 and SYVN1 mediate the inhibition of GLUD1 in HCC,especially in HBV-related tumors.

关 键 词：hepatocellular carcinoma HBX GLUD1 LASP1 SYVN1 

分 类 号：R512.62[医药卫生—内科学]