Evidence map›Paper›PMID 41366477›Full record

ArticleEuropean journal of medical research2025

UHRF1 silencing restrained the malignant phenotype of melanoma cells by inhibiting the HOXA9/HIF-1α axis-mediated glycolysis.

Yang Gao, Caixia Hu, Shaoqian Jiang, Lijing Lv, Yan Zhang, Yi Cheng

Abstract read
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Article in European journal of medical research, 2025. 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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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Yang GaoDepartment of Interventional Radiology, Hebei Children's Hospital, Hebei Provincial Clinical Research Center for Child Health and Disease, Hebei Provincial Key Laboratory of Pediatric, Shijiazhuang, 050031, Hebei, China.
Caixia HuDepartment of Dermotology, The Fourth Hospital of Hebei Medical University, No.12 Health Road, Chang'an District, Shijiazhuang, 050017, Hebei, China.
Shaoqian JiangDepartment of Dermotology, The Fourth Hospital of Hebei Medical University, No.12 Health Road, Chang'an District, Shijiazhuang, 050017, Hebei, China.
Lijing LvDepartment of Dermotology, The Fourth Hospital of Hebei Medical University, No.12 Health Road, Chang'an District, Shijiazhuang, 050017, Hebei, China.
Yan ZhangDepartment of Dermotology, The Fourth Hospital of Hebei Medical University, No.12 Health Road, Chang'an District, Shijiazhuang, 050017, Hebei, China.
Yi ChengDepartment of Dermotology, The Fourth Hospital of Hebei Medical University, No.12 Health Road, Chang'an District, Shijiazhuang, 050017, Hebei, China. m15833913562@163.com.

Funding

the Medical Science Research Project of Hebei 20160158
6 · The paper itself

Abstract

backgroundUbiquitin-like with PHD and ring finger domains 1 (UHRF1) promotes DNA methylation of tumor suppressor genes, contributing to cancer development. Given its observed upregulation in melanoma, this study aimed to its functional roles and elucidate the underlying molecular mechanisms.

methodsUHRF1 protein levels was evaluated in human melanoma tissues and cell lines. Gain- and loss-of-function experiments were conducted in two melanoma cell lines (A357 and SK-MEL-28), and cell proliferation, invasion, and apoptosis were examined. Homeobox A9 (HOXA9) promoter methylation was assessed using methylation-specific PCR. HOXA9-mediated transcriptional regulation of hypoxia-inducible factor 1α (HIF-1α) was validated in melanoma cells. Glycolysis was evaluated by detecting glucose uptake, lactate production, ATP levels, and extracellular acidification rate (ECAR). Additionally, a xenograft model was established using UHRF1-knockdown A375 cells, and tumor growth was monitored in nude mice.

resultsUHRF1 was significantly upregulated in melanoma tissues and cell lines. UHRF1 overexpression facilitated melanoma cell proliferation and invasion and inhibited apoptosis, while UHRF1 silencing led to an opposite result. Mechanistically, UHRF1 promoted DNMT1-mediated HOXA9 promoter methylation and inhibited HOXA9 expression in melanoma cells. HOXA9 transcriptionally inhibited HIF-1α expression in melanoma cells. Consequently, UHRF1 overexpression upregulated HIF-1α expression in melanoma cells, thus promoting glycolysis in melanoma cells. Moreover, HIF-1α overexpression neutralized the promoting effects of UHRF1 silencing on proliferation, invasion, and glycolysis. In addition, UHRF1 silencing suppressed melanoma growth in mice.

conclusionUHRF1 silencing restrained the malignant phenotype of melanoma cells by inhibiting the HOXA9/HIF-1α axis-mediated glycolysis, thus suppressing tumor growth in mice.

Indexed as

CCAAT-Enhancer-Binding ProteinsHomeodomain ProteinsHypoxia-Inducible Factor 1, alpha SubunitMelanomaUbiquitin-Protein LigasesAnimalsApoptosisCell Line, TumorCell ProliferationDNA MethylationFemaleGene Expression Regulation, NeoplasticGene SilencingGlycolysisHumansMaleCCAAT-Enhancer-Binding ProteinsHIF1A protein, humanhomeobox protein HOXA9Homeodomain ProteinsHypoxia-Inducible Factor 1, alpha SubunitUbiquitin-Protein LigasesUHRF1 protein, humanGlycolysisHIF-1αHOXA9MelanomaUHRF1

Identifiers

PMID41366477
PMCPMC12750810

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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.