2. Academic Validation
  3. UBXN1 promotes liver tumorigenesis by regulating mitochondrial homeostasis

UBXN1 promotes liver tumorigenesis by regulating mitochondrial homeostasis

  • J Transl Med. 2024 May 21;22(1):485. doi: 10.1186/s12967-024-05208-5.
Kun Jiao # 1 2,  Guiqin Xu # 2,  Yun Liu 2,  Zhaojuan Yang 2,  Lvzhu Xiang 2,  Zehong Chen 2,  Chen Xu 2,  You Zuo 2,  Zhibai Wu 2,  Ningqian Zheng 2,  Wangjie Xu 3,  Li Zhang 4,  Yongzhong Liu 5 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 2 State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 3 Laboratory Animal Center, Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 4 State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China. zhangli@shsci.org.
  • 5 State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China. liuyzg@shsci.org.
  • 6 State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China. liuyzg@shsci.org.
  • # Contributed equally.
PMID: 38773518 DOI: 10.1186/s12967-024-05208-5
Abstract

Background: The maintenance of mitochondrial homeostasis is critical for tumor initiation and malignant progression because it increases tumor cell survival and growth. The molecular events controlling mitochondrial integrity that facilitate the development of hepatocellular carcinoma (HCC) remain unclear. Here, we report that UBX domain-containing protein 1 (UBXN1) hyperactivation is essential for mitochondrial homeostasis and liver tumorigenesis.

Methods: Oncogene-induced mouse liver tumor models were generated with the Sleeping Beauty (SB) transposon delivery system. Assessment of HCC cell growth in vivo and in vitro, including tumour formation, colony formation, TUNEL and FACS assays, was conducted to determine the effects of UBXN1 on HCC cells, as well as the involvement of the UBXN1-prohibitin (PHB) interaction in mitochondrial function. Coimmunoprecipitation (Co-IP) was used to assess the interaction between UBXN1 and PHB. Liver hepatocellular carcinoma (LIHC) datasets and HCC patient samples were used to assess the expression of UBXN1.

Results: UBXN1 expression is commonly upregulated in human HCCs and mouse liver tumors and is associated with poor overall survival in HCC patients. UBXN1 facilitates the growth of human HCC cells and promotes mouse liver tumorigenesis driven by the NRas/c-Myc or c-Myc/shp53 combination. UBXN1 interacts with the inner mitochondrial membrane protein PHB and sustains PHB expression. UBXN1 inhibition triggers mitochondrial damage and liver tumor cell Apoptosis.

Conclusions: UBXN1 interacts with PHB and promotes mitochondrial homeostasis during liver tumorigenesis.

Keywords

Apoptosis; Hepatocellular carcinoma; Mitochondrial homeostasis; PHB; UBXN1.

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