2. Academic Validation
  3. Targeting VPS72 inhibits ACTL6A/MYC axis activity in hepatocellular carcinoma progression

Targeting VPS72 inhibits ACTL6A/MYC axis activity in hepatocellular carcinoma progression

  • Hepatology. 2023 Jan 13. doi: 10.1097/HEP.0000000000000268.
Furong Liu 1 2,  Zhibin Liao 1 2,  Lu Qin 3,  Ze Zhang 1 2,  Qiaofeng Zhang 1 2,  Shenqi Han 1 2,  Weifeng Zeng 1 2,  Hongwei Zhang 1 2,  Yachong Liu 1 2,  Jia Song 1 2,  Wei Chen 1 2,  He Zhu 1 2,  Huifang Liang 1 2,  Xiaoping Chen 1 2,  Bixiang Zhang 1 2,  Zhanguo Zhang 1 2
Affiliations

Affiliations

  • 1 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • 2 Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei 430030, China.
  • 3 Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
PMID: 36631007 DOI: 10.1097/HEP.0000000000000268
Abstract

Background and aims: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease that is caused largely by genomic copy number variations (CNVs). Herein, the mechanistic and therapeutically targeted role of VPS72, a novel CNV cis-driven gained gene identified by genome-wide CNV 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.

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