ArticleBMC cancer2015
URG4/URGCP enhances the angiogenic capacity of human hepatocellular carcinoma cells in vitro via activation of the NF-κB signaling pathway.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Modulating hypertrophic scar formation by targeting endothelial transient receptor potential vanilloid-1/nuclear factor kappa-B/interleukin-6 axis to regulate angiogenesis.Burns & trauma · 2026Article
- Immunohistochemical Expression of Upregulated Gene 4 Protein Expression (URG4/URGCP) and Its Association with 5-Year Survival in Patients with Colon Adenocarcinoma.Journal of clinical medicine · 2023Article
- Hsa_circ_0021727 (circ-CD44) promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway.Cell death & disease · 2023Article
- Effects of Uremic Clearance Granules on p38 MAPK/NF-κB Signaling Pathway, Microbial and Metabolic Profiles in End-Stage Renal Disease Rats Receiving Peritoneal Dialysis.Drug design, development and therapy · 2022Article
- Epigenome-wide association study of maternal hemoglobin A1c in pregnancy and cord blood DNA methylation.Epigenomics · 2021Article
- Article
- Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer-from Tumor Development to Therapeutic Implications.Cancers · 2019Review
- MicroRNA-708-5p affects proliferation and invasion of osteosarcoma cells by targeting URGCP.Experimental and therapeutic medicine · 2019Article
- Inflammatory cytokine-induced expression of MASTL is involved in hepatocarcinogenesis by regulating cell cycle progression.Oncology letters · 2019Article
- Downregulation of miR-16 via URGCP pathway contributes to glioma growth.Scientific reports · 2017Article
- SP1 is a transcriptional regulator of URG-4/URGCP gene in hepatocytes.Molecular and cellular biochemistry · 2016Article
- Triptolide Inhibits Invasion and Tumorigenesis of Hepatocellular Carcinoma MHCC-97H Cells Through NF-κB Signaling.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- Anti-proliferative and anti-invasive effects of ferulic acid in TT medullary thyroid cancer cells interacting with URG4/URGCP.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- URG4 expression is a novel prognostic factor for the progression of nasopharyngeal carcinoma and overall survival of patient.OncoTargets and therapy · 2016Article
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Authors and funding
12 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAngiogenesis is essential for tumor growth. Hepatocellular carcinoma (HCC) is characterized by hypervascularity; high levels of angiogenesis are associated with poor prognosis and a highly invasive phenotype in HCC. Up-regulated gene-4 (URG4), also known as upregulator of cell proliferation (URGCP), is overexpressed in multiple tumor types and has been suggested to act as an oncogene. This study aimed to elucidate the effect of URG4/URGCP on the angiogenic capacity of HCC cells in vitro.
methodsExpression of URG4/URGCP in HCC cell lines and normal liver epithelial cell lines was examined by Western blotting and quantitative real-time PCR. URG4/URGCP was stably overexpressed or transiently knocked down using a shRNA in two HCC cell lines. The human umbilical vein endothelial cell (HUVEC) tubule formation and Transwell migration assays and chicken chorioallantoic membrane (CAM) assay were used to examine the angiogenic capacity of conditioned media from URG4/URGCP-overexpressing and knockdown cells. A luciferase reporter assay was used to examine the transcriptional activity of nuclear factor kappa - light - chain - enhancer of activated B cells (NF-κB). NF-κB was inhibited by overexpressing degradation-resistant mutant inhibitor of κB (IκB)-α. Expression of vascular endothelial growth factor C (VEGFC), tumor necrosis factor-α (TNFα), interleukin (IL)-6, IL-8 and v-myc avian myelocytomatosis viral oncogene homolog (MYC) were examined by quantitative real-time PCR; VEGFC protein expression was analyzed using an ELISA.
resultsURG4/URGCP protein and mRNA expression were significantly upregulated in HCC cell lines. Overexpressing URG4/URGCP enhanced - while silencing URG4/URGCP decreased - the capacity of HCC cell conditioned media to induce HUVEC tubule formation and migration and neovascularization in the CAM assay. Furthermore, overexpressing URG4/URGCP increased - whereas knockdown of URG4/URGCP decreased - VEGFC expression, NF-κB transcriptional activity, the levels of phosphorylated (but not total) IκB kinase (IKK) and IκB-α, and expression of TNFα, IL-6, IL-8 and MYC in HCC cells. Additionally, inhibition of NF-κB activity in HCC cells abrogated URG4/URGCP-induced NF-κB activation and angiogenic capacity.
conclusionsThis study suggests that URG4/URGCP plays an important pro-angiogenic role in HCC via a mechanism linked to activation of the NF-κB pathway; URG4/URGCP may represent a potential target for anti-angiogenic therapy in HCC.
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