ArticleOncotarget2016
Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Beyond VEGF: AEG-1/MTDH as a Systems-Level Orchestrator of Angiogenesis in Hepatocellular Carcinoma.Cells · 2026Review
- HIF2α negatively regulates MYCN protein levels and promotes a low-risk noradrenergic phenotype in neuroblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Bridging Immune Evasion and Vascular Dynamics for Novel Therapeutic Frontiers in Hepatocellular Carcinoma.Cancers · 2025Review
- Review
- Hypoxia-Inducible Factor-2α Promotes Liver Fibrosis by Inducing Hepatocellular Death.International journal of molecular sciences · 2024Article
- Review
- Cited2 inhibited hypoxia-induced proliferation and migration of PASMCs via the TGF-β1/Cited2/PPARγ pathway.Iranian journal of basic medical sciences · 2024Article
- Review
- Inflammatory processes involved in NASH-related hepatocellular carcinoma.Bioscience reports · 2023Review
- HIF and MYC signaling in adrenal neoplasms of the neural crest: implications for pediatrics.Frontiers in endocrinology · 2023Review
- HIF-2α regulates proliferation, invasion, and metastasis of hepatocellular carcinoma cellsFrontiers in oncology · 2022Article
- Review
- Upregulation of Nogo-B by hypoxia inducible factor-1 and activator protein-1 in hepatocellular carcinoma.Cancer science · 2021Article
- Prognostic and clinicopathological significance of hypoxia-inducible factors 1α and 2α in hepatocellular carcinoma: a systematic review with meta-analysis.Therapeutic advances in medical oncology · 2021Article
- CITED2 and the modulation of the hypoxic response in cancer.World journal of clinical oncology · 2020Review
- Hypoxia‑inducible factors in hepatocellular carcinoma (Review).Oncology reports · 2020Review
- Stabilization of HIF-2α impacts pancreas growth.Scientific reports · 2018Article
- Hepatitis B virus upregulates GP73 expression by activating the HIF-2α signaling pathway.Oncology letters · 2018Article
- Prognostic Role of Hypoxia-Inducible Factor-2α Tumor Cell Expression in Cancer Patients: A Meta-Analysis.Frontiers in oncology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of HIF-2α in hepatocellular carcinoma (HCC) is unclear. The aim of the present study was to investigate the expression pattern and role of HIF-2α in HCC patients. Immunohistochemical staining and western blotting analyses were applied to detect the protein level of HIF-2α in 206 paired HCC and peritumoral tissues. Kaplan-Meier survival and Cox proportional hazard regression analyses were performed to identify risk factors for overall survival and recurrence-free survival in these patients. The function of HIF-2α was studied in HCC cells and in vivo models. We found that the protein levels of HIF-2α in HCC tissues were lower than in peritumoral tissues, and were negatively correlated with tumor size (P < 0.05). Kaplan-Meier survival and univariate analysis revealed that HCC patients with high HIF-2α protein levels had longer overall survival (P < 0.05). Over-expression of HIF-2α induced apoptosis in HCC cells and increased the levels of pro-apoptotic proteins, Bak, ZBP-89 and PDCD4, whereas the inhibition of HIF-2α expression achieved opposite results. The findings were confirmed in a mouse HCC xenograft model. In conclusion, our study revealed that HIF-2α was decreased and played an anti-tumorigenic role in HCC.
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Registered trials
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.