单位：[1]Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China外科学系肝脏外科华中科技大学同济医学院附属同济医院[2]Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China[3]Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China华中科技大学同济医学院附属协和医院
Background and Aims:HCC is a highly heterogeneous disease that is caused largely by genomic copy number variations. Herein, the mechanistic and therapeutically targeted role of vacuolar protein sorting 72 homologue (VPS72), a novel copy number variation cis-driven gained gene identified by genome-wide copy number variation and transcriptome analyses in HCC, is not well understood.Approach and Results:First, overexpression of VPS72 enhanced the initiation and progression of HCC in vitro and in vivo. Mechanistically, VPS72 interacted with the oncoproteins MYC and actin-like 6A (ACTL6A) and promoted the formation of the ACTL6A/MYC complex. Furthermore, ACTL6A regulated VPS72 protein stability by weakening the interaction between tripartite motif containing 21 (TRIM21) and VPS72. Thus, the interaction between VPS72 and ACTL6A enhanced the affinity of MYC for its target gene promoters and promoted their transcription, thereby contributing to HCC progression, which was inhibited by adeno-associated virus serotype 8 (AAV8)-mediated short hairpin RNA (shRNA) against VPS72.Conclusions:This study reveals the molecular mechanism of ACTL6A/VPS72/MYC in HCC, providing a theoretical basis and therapeutic target for this malignancy.
基金：
Furong Liu, Zhibin Liao, and Lu Qin contributed equally to this work. Ze Zhang, Bixiang Zhang, and Xiaoping Chen conceived this study. Ze Zhang, Bixiang Zhang, and Xiaoping Chen provided financial and administrative support. Furong Liu and Zhibin Liao cond
第一作者单位：[1]Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China[2]Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China
共同第一作者：
通讯作者：
通讯机构：[1]Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China[2]Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, China[*1]Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, 1095 Jiefang Avenue, 430030 Wuhan, China.
推荐引用方式(GB/T 7714)：
Liu Furong,Liao Zhibin,Qin Lu,et al.Targeting VPS72 inhibits ACTL6A/MYC axis activity in HCC progression[J].HEPATOLOGY.2023,78(5):1384-1401.doi:10.1097/HEP.0000000000000268.
医学