2. Academic Validation
  3. UBXD8 promotes lung cancer progression and activates the HIF-1α pathway

UBXD8 promotes lung cancer progression and activates the HIF-1α pathway

  • Biochem Pharmacol. 2025 Jun 23:240:117078. doi: 10.1016/j.bcp.2025.117078.
Miaomiao Wang 1,  Yingsen Guo 1,  Yunzhang Liu 1,  Shanpeng Ma 1,  Jingfang Zhang 2,  Yun Li 1,  Hongbing Liu 1,  Ling Lu 3
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China; Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao, China.
  • 2 Department of Pathology, Shandong First Medical University, Jinan, Shandong 250062, China.
  • 3 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China; Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao, China. Electronic address: linglu@ouc.edu.cn.
PMID: 40562127 DOI: 10.1016/j.bcp.2025.117078
Abstract

UBXD8, a ubiquitin regulatory X domain-containing protein, is highly expressed in advanced tumor stages and is associated with reduced survival rates. In this study, we found that knockdown of UBXD8 resulted in a significant decline in non-small cell lung Cancer (NSCLC) cell proliferation and migratory capacity in vitro, as well as a reduction in tumor growth within xenograft models, suggesting its potential as a prognostic marker. Moreover, we identify UBXD8 as a positive modulator of hypoxia inducible factor (HIF) signaling. UBXD8 contributed to the stabilization and increased expression of HIF-1α protein, leading to the upregulation of its downstream target genes. Furthermore, metabolic analysis indicated that the absence of UBXD8 elevated levels of unsaturated fatty acids, underscoring its function in lipid metabolic processes. Collectively, these findings revealed a significant role for UBXD8 in tumor development and HIF-1α regulation.

Keywords

Cancer; HIF-1α; Hypoxia; Lipid metabolism; UBXD8.

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