We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Elevated expression of HIGD1A drives hepatocellular carcinoma progression by regulating polyamine metabolism through c-Myc–ODC1 nexus.
- Authors
Zhang, Haixing; Li, Xiaoran; Liu, Ziying; Lin, Zimo; Huang, Kuiyuan; Wang, Yiran; Chen, Yu; Liao, Leyi; Wu, Leyuan; Xie, Zhanglian; Hou, Jinlin; Zhang, Xiaoyong; Liu, Hongyan
- Abstract
Background: Hypoxia contributes to cancer progression through various molecular mechanisms and hepatocellular carcinoma (HCC) is one of the most hypoxic malignancies. Hypoxia-inducible gene domain protein-1a (HIGD1A) is typically induced via epigenetic regulation and promotes tumor cell survival during hypoxia. However, the role of HIGD1A in HCC remains unknown. Methods: HIGD1A expression was determined in 24 pairs of human HCC samples and para-tumorous tissues. Loss-of-function experiments were conducted both in vivo and in vitro to explore the role of HIGD1A in HCC proliferation and metastasis. Results: Increased HIGD1A expression was found in HCC tissues and cell lines, which was induced by hypoxia or low-glucose condition. Moreover, HIGD1A knockdown in HCC cells arrested the cell cycle at the G2/M phase and promoted hypoxia-induced cell apoptosis, resulting in great inhibition of cell proliferation, migration, and invasion, as well as tumor xenograft formation. Interestingly, these anti-tumor effects were not observed in normal hepatocyte cell line L02. Further, HIGD1A knockdown suppressed the expression of ornithine decarboxylase 1 (ODC1), a rate-limiting enzyme of polyamine metabolism under c-Myc regulation. HIGD1A was found to bind with the c-Myc promoter region, and its knockdown decreased the levels of polyamine metabolites. Consistently, the inhibitory effect on HCC phenotype by HIGD1A silencing could be reversed by overexpression of c-Myc or supplementation of polyamines. Conclusions: Our results demonstrated that HIGD1A activated c-Myc–ODC1 nexus to regulate polyamine synthesis and to promote HCC survival and malignant phenotype, implying that HIGD1A might represent a novel therapeutic target for HCC.
- Subjects
HEPATOCELLULAR carcinoma; ORNITHINE decarboxylase; ENZYME metabolism; METABOLISM; CELL cycle
- Publication
Cancer & Metabolism, 2024, Vol 12, Issue 1, p1
- ISSN
2049-3002
- Publication type
Article
- DOI
10.1186/s40170-024-00334-6