ArticleOncology reports2019
Inhibition of neddylation modification by MLN4924 sensitizes hepatocellular carcinoma cells to sorafenib.
Article in Oncology reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Deciphering the roles of neddylation modification in hepatocellular carcinoma: Molecular mechanisms and targeted therapeutics.Genes & diseases · 2025Review
- NUB1 reduction promotes PCNA-mediated tumor growth by disturbing the PCNA polyubiquitination/NEDDylation in hepatocellular carcinoma cells.Cell death & disease · 2025Article
- Machine Learning-Derived Neddylation Gene Signature for Predicting Prognosis and Immunotherapy Benefits in Colorectal Cancer.ImmunoTargets and therapy · 2025Article
- Effects of neddylation on viral infection: an overview.Archives of virology · 2023Review
- Elevated FBXL6 expression in hepatocytes activates VRK2-transketolase-ROS-mTOR-mediated immune evasion and liver cancer metastasis in mice.Experimental & molecular medicine · 2023Article
- Molecular mechanisms of autophagy and implications in liver diseases.Liver research (Beijing, China) · 2023Review
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- Small Molecule Inhibitors for Hepatocellular Carcinoma: Advances and Challenges.Molecules (Basel, Switzerland) · 2022Review
- Cullin neddylation inhibitor attenuates hyperglycemia by enhancing hepatic insulin signaling through insulin receptor substrate stabilization.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Pevonedistat Suppresses Pancreatic Cancer GrowthFrontiers in oncology · 2022Article
- Critical signaling pathways governing hepatocellular carcinoma behavior; small molecule-based approaches.Cancer cell international · 2021Review
- [Research progress of neural precursor cells-expressed developmentally down-regulated protein-8 in liver diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Article
- [Effects of Cullin1 on the Biological Characteristics of Lung Adenocarcinoma A549 and H1395 Cells].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Article
- The Effect of Neddylation Blockade on Slug-Dependent Cancer Cell Migration Is Regulated by p53 Mutation Status.Cancers · 2021Article
- Identification of the HECT E3 ligase UBR5 as a regulator of MYC degradation using a CRISPR/Cas9 screen.Scientific reports · 2020Article
- The Potential of MLN3651 in Combination with Selumetinib as a Treatment for Merlin-Deficient Meningioma.Cancers · 2020Article
- Neddylation: A Versatile Pathway Takes on Chronic Liver Diseases.Frontiers in medicine · 2020Review
- Article
- Degradation of splicing factor SRSF3 contributes to progressive liver disease.The Journal of clinical investigation · 2019Article
Corrections and comments
- Retraction · 2025-01-13Author Unresponsive · Concerns/Issues about Data · Concerns/Issues about Article · Concerns/Issues about Results and/or Conclusions · Duplication of Data · Error in Data · Euphemisms for Duplication · Investigation by Journal/Publisher · Unreliable Data · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib remains the standard care for patients with hepatocellular carcinoma (HCC) even though it has low antitumor efficacy. Protein neddylation is abnormally activated in many types of human cancer. However, whether dysregulation of neddylation is involved in HCC progression and whether targeting neddylation sensitizes HCC cells to sorafenib need to be ascertained. In the present study, it was demonstrated that high expression of neddylation components, neural precursor cell expressed, developmentally downregulated 8 (NEDD8) and NEDD8‑activating enzyme 1 (NAE1), were associated with poor survival of patients with HCC. Inhibition of neddylation by MLN4924, a small‑molecule inhibitor of NAE1, significantly inhibited HCC growth, reduced clonogenic survival, increased apoptosis, and decreased migration capacity. Sorafenib alone exhibited minimal anticancer efficacy. However, a combination of sorafenib with MLN4924 at a low concentration significantly enhanced the inhibition of cell proliferation and migration as well as the induction of apoptosis induced by sorafenib. In vivo HCC xenograft mouse models also showed that MLN4924 increased the antitumor efficacy of sorafenib. Mechanistically, MLN4924 enhanced the antitumor activity of sorafenib in HCC cells via upregulation of cullin‑RING E3 ubiquitin ligase (CRL)/Skp1‑Cullin1‑F box (SCF) E3 ubiquitin ligase substrates p21, p27, Deptor and IκBɑ. Taken together, these findings suggest that combination therapy of MLN4924 with sorafenib appears to present an additive effect with a maximal in the treatment of 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.