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ArticleMolecular biology reports2026

Hypoxia-induced GP73 promotes the Warburg effect in hepatocellular carcinoma via HIF-1α.

Mierkamilijiang Abudureheman, Diwen Zhu, Weixin Ren

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Article in Molecular biology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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3 authors.

Mierkamilijiang AbudurehemanDepartment of Interventional Radiology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
Diwen ZhuDepartment of Interventional Radiology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
Weixin RenDepartment of Interventional Radiology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China. rwx1031@163.com.

Funding

This study was supported by the Tianshan Talents Program for Medical and Health High-Level Talents Training Plan of the Health Commission of Xinjiang Uygur Autonomous Region TSYC202301B032
6 · The paper itself

Abstract

backgroundTransarterial chemoembolization (TACE)-induced hypoxia is a key driver of hepatocellular carcinoma (HCC) progression. This study investigated whether Golgi protein 73 (GP73) drives the Warburg effect and epithelial-mesenchymal transition (EMT) via hypoxia-inducible factor-1α (HIF-1α) under hypoxia, thereby promoting HCC malignancy.

methodsHepG2 cells were exposed to hypoxia (1% O₂). Lentivirus-mediated GP73 overexpression (LV-GP73) and siRNA-mediated HIF-1α knockdown (si-HIF-1α) were established. Four groups were compared: H + LV-NC (negative control), H + LV-GP73, H + LV-GP73 + si-NC, and H + LV-GP73 + si-HIF-1α. Cell proliferation, apoptosis, migration, and invasion were assessed by colony formation, flow cytometry, and Transwell assays. Glycolysis and mitochondrial respiration were evaluated by biochemical kits and Seahorse XFe24 Analyzer. Protein levels were detected by Western blotting. Clinical validation was performed in peripheral blood mononuclear cells (PBMCs) from 169 HCC patients who underwent TACE.

resultsGP73 overexpression significantly enhanced colony formation, migration, invasion, glucose consumption, lactate production, LDH activity, ATP levels, and extracellular acidification rate, while decreasing apoptosis (P < 0.05). It also showed a decreasing trend in oxygen consumption rate, indicating Warburg effect activation. It also upregulated HIF-1α, glycolytic enzymes (HK2, SLC2A1, LDHA, PGK1), and Vimentin, but downregulated E-cadherin (P < 0.05). Notably, HIF-1α knockdown reversed all these pro-tumorigenic phenotypes, metabolic reprogramming, and molecular changes. Clinical validation further confirmed that PBMCs from TACE-resistant patients exhibited significantly elevated GP73, HIF-1α, and HK2 expression at both mRNA and protein levels (all P < 0.001), consistent with the in vitro findings.

conclusionsUnder hypoxia, GP73 promotes the Warburg effect and EMT through HIF-1α stabilization, facilitating HCC progression. The GP73-HIF-1α axis is a critical mediator of TACE resistance and a potential therapeutic target. PBMC-based detection of this pathway may serve as a non-invasive strategy for monitoring TACE resistance risk.

Indexed as

Carcinoma, HepatocellularHypoxia-Inducible Factor 1, alpha SubunitLiver NeoplasmsMembrane ProteinsWarburg Effect, OncologicApoptosisCell HypoxiaCell Line, TumorCell MovementCell ProliferationEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticGlycolysisHep G2 CellsHumansGOLM1 protein, humanHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMembrane ProteinsEpithelial-mesenchymal transitionGP73Hepatocellular carcinomaHypoxia-inducible factor-1αWarburg effect

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.