ArticleScientific reports2017
Downregulation of UHRF1 increases tumor malignancy by activating the CXCR4/AKT-JNK/IL-6/Snail signaling axis in hepatocellular carcinoma cells.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- STAT3 as a Candidate Shared Regulator of the CXCR4/CXCL12 and CXCR5/CXCL13 Homing Axes in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2026Review
- CXCR4: A Promising Novel Strategy for Lung Cancer Treatment.Biomolecules · 2026Review
- Expression Profile of Serum CircFUNDC1 and CircUHRF1 Can Differentiate Between Colorectal Cancer and Inflammatory Bowel Diseases (Ulcerative Colitis and Crohn's Disease).Journal of clinical laboratory analysis · 2025Article
- Review
- Article
- Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells.Open medicine (Warsaw, Poland) · 2023Article
- Interleukin-6 at the Host-Tumor Interface: STAT3 in Biomolecular Condensates in Cancer Cells.Cells · 2022Review
- The multi-functionality of UHRF1: epigenome maintenance and preservation of genome integrity.Nucleic acids research · 2021Review
- Article
- The malignancy of liver cancer cells is increased by IL-4/ERK/AKT signaling axis activity triggered by irradiated endothelial cells.Journal of radiation research · 2020Article
- Article
- Hydrogen peroxide inducible clone-5 sustains NADPH oxidase-dependent reactive oxygen species-c-jun N-terminal kinase signaling in hepatocellular carcinoma.Oncogenesis · 2019Article
- Antitumor activity of Raddeanin A is mediated by Jun amino-terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma.Cancer science · 2019Article
- Irradiated endothelial cells modulate the malignancy of liver cancer cells.Oncology letters · 2019Article
- Targeting the SET and RING-associated (SRA) domain of ubiquitin-like, PHD and ring finger-containing 1 (UHRF1) for anti-cancer drug development.Oncotarget · 2018Review
- The deleterious interplay between tumor epithelia and stroma in cholangiocarcinoma.Biochimica et biophysica acta. Molecular basis of disease · 2018Review
- Targeting microRNA/UHRF1 pathways as a novel strategy for cancer therapy.Oncology letters · 2018Article
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Authors and funding
8 authors.
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Abstract
UHRF1 (ubiquitin-like, with PHD and RING finger domains 1) plays a crucial role in DNA methylation, chromatin remodeling and gene expression and is aberrantly upregulated in various types of human cancers. However, the precise role of UHRF1 in cancer remains controversial. In this study, we observed that hypoxia-induced downregulation of UHRF1 contributes to the induction of the epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma cells. By negatively modulating UHRF1 expression, we further showed that UHRF1 deficiency in itself is sufficient to increase the migratory and invasive properties of cells via inducing EMT, increasing the tumorigenic capacity of cells and leading to the expansion of cancer stem-like cells. Epigenetic changes caused by UHRF1 deficiency triggered the upregulation of CXCR4, thereby activating AKT and JNK to increase the expression and secretion of IL-6. In addition, IL-6 readily activated the JAK/STAT3/Snail signaling axis, which subsequently contributed to UHRF1 deficiency-induced EMT. Our results collectively demonstrate that UHRF1 deficiency may play a pivotal role in the malignant alteration of cancer cells.
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