ArticleOncogene2020
HIPK2 suppresses tumor growth and progression of hepatocellular carcinoma through promoting the degradation of HIF-1α.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Silencing of Homeodomain-Interacting Protein Kinase 2 (HIPK2) Induces Anti-Adipogenic Effects in 3T3-L1 Adipocytes.Current issues in molecular biology · 2026Article
- HIPK2 exhibits context dependent dualistic effects and combinatorial inhibition of HIPK2-NLK-MAPK11 axis manifests synergism against gastric cancer.Human cell · 2026Article
- Unraveling the role of HIF2α in melanoma progression and epithelial-mesenchymal transition.Scientific reports · 2025Article
- New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025Review
- HIPK2 in Colon Cancer: A Potential Biomarker for Tumor Progression and Response to Therapies.International journal of molecular sciences · 2024Review
- Molecular profiling of a bladder cancer with very high tumour mutational burden.Cell death discovery · 2024Article
- Alleviating hypoxia to improve cancer immunotherapy.Oncogene · 2023Review
- HIPK2 in Angiogenesis: A Promising Biomarker in Cancer Progression and in Angiogenic Diseases.Cancers · 2023Review
- A molecular study of pediatric pilomyxoid and pilocytic astrocytomas: Genome-wide copy number screening, retrospective analysis of clinicopathological features and long-term clinical outcome.Frontiers in oncology · 2023Article
- miR-4653-3p overexpression is associated with a poor prognosis of pancreatic ductal adenocarcinoma via HIPK2 downregulation.Scientific reports · 2022Article
- The cuproptosis-related gene signature serves as a potential prognostic predictor for ovarian cancer using bioinformatics analysis.Annals of translational medicine · 2022Article
- Phosphoproteomic Analysis of FLCN Inactivation Highlights Differential Kinase Pathways and Regulatory TFEB Phosphoserines.Molecular & cellular proteomics : MCP · 2022Article
- Hypoxia-inducible factor-1α: A critical target for inhibiting the metastasis of hepatocellular carcinoma.Oncology letters · 2022Review
- Article
- Integrated Analysis of the Altered lncRNA, microRNA, and mRNA Expression in HBV-Positive Hepatocellular Carcinoma.Life (Basel, Switzerland) · 2022Article
- Exosomal miR-224-5p from Colorectal Cancer Cells Promotes Malignant Transformation of Human Normal Colon Epithelial Cells by Promoting Cell Proliferation through Downregulation of CMTM4.Oxidative medicine and cellular longevity · 2022Article
- MiR-423-5p activated by E2F1 promotes neovascularization in diabetic retinopathy by targeting HIPK2.Diabetology & metabolic syndrome · 2021Article
- Lysophosphatidic Acid Receptor 6 (LPAR6) Is a Potential Biomarker Associated with Lung Adenocarcinoma.International journal of environmental research and public health · 2021Article
- Overexpression of microRNA-100-5p attenuates the endothelial cell dysfunction by targeting HIPK2 under hypoxia and reoxygenation treatment.Journal of molecular histology · 2021Article
- The Interplay Between Tumor Suppressor p53 and Hypoxia Signaling Pathways in Cancer.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant angiogenesis of hepatocellular carcinoma (HCC) leads to tumor growth and local or distant metastasis. Uncovering the underlying mechanisms for the neoangiogenesis of HCC can provide novel potential therapeutic targets in the clinic. Here, we reported that serine/threonine homeodomain-interacting protein kinase 2 (HIPK2) was frequently downregulated in HCC tissues compared with the adjacent normal tissues, and patients with lower HIPK2 protein expression were associated with worse overall survival. Both in vitro and in vivo, HIPK2 inhibited the migration of HCC cells, as well as tumor growth and metastasis in xenograft and orthotopic syngeneic HCC mouse models. Furthermore, HIPK2 inhibited the angiogenesis in HCC tumors. Under the hypoxic condition, HIPK2 knockdown enhanced the angiogenesis and the key regulator, HIF-1α signaling pathway; however, HIPK2 overexpression downregulated the tumoral angiogenesis and HIF-1α signaling. In HCC cells, HIPK2 could directly bind to HIF-1α and stimulate the ubiquitination of HIF-1α for proteasomal degradation. HIF-1α knockout partially rescued the promoting effect of HIPK2 depletion on angiogenesis and tumor growth. In conclusion, the downregulation of HIPK2 could enhance the angiogenesis in HCC through inducing the HIF-1α pathway, and further contribute to tumor growth and metastasis, which may provide a novel therapeutic strategy for HCC.
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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.