ArticleCancer research2020
SUMOylation of E2F1 Regulates Expression of EZH2.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 24 citations in OpenAlex.
- Amyloid Precursor Protein Processing Links Female Urgency Urinary Incontinence with Alzheimer's Disease: Implications for Treatment.International journal of molecular sciences · 2026Article
- UBA2: the gatekeeper of the sumoylation pathway and its multifaceted roles in human diseases and therapeutic prospects.Clinical and experimental medicine · 2026Review
- Blockage of SUMO E1 enzyme inhibits ocular lens fibrosis by mediating SMAD4 SUMOylation.Genes & diseases · 2026Article
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Comparative Proteomic Profiling of Adrenocortical Neoplasia Using Mass Spectrometry.Journal of proteome research · 2025Article
- Article
- Epithelial-mesenchymal transition in colorectal cancer metastasis and progression: molecular mechanisms and therapeutic strategies.Cell death discovery · 2025Review
- Enhancer zeste homolog 2 (EZH2) targeting by small interfering RNA (siRNA); recent advances and prospect.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- NSUN2-mediated HCV RNA m5C Methylation Facilitates Viral RNA Stability and Replication.Genomics, proteomics & bioinformatics · 2025Article
- UBA2 SUMOylates NQO1 and promotes the proliferation of hepatocellular carcinoma by modulating the MAPK pathway.Cancer science · 2024Article
- Regulation of Enhancers by SUMOylation Through TFAP2C Binding and Recruitment of HDAC Complex to the Chromatin.Research square · 2024Article
- Gastric Cancer in the Era of Epigenetics.International journal of molecular sciences · 2024Review
- Role of non-canonical post-translational modifications in gastrointestinal tumors.Cancer cell international · 2023Review
- SENP5 deteriorates traumatic brain injury via SUMO2-dependent suppression of E2F1 SUMOylation.Acta biochimica et biophysica Sinica · 2023Article
- SUMOylation inhibition enhances multiple myeloma sensitivity to lenalidomide.Cancer gene therapy · 2023Article
- Regulation of SUMOylation on RNA metabolism in cancers.Frontiers in molecular biosciences · 2023Review
- Sevoflurane Offers Neuroprotection in a Cerebral Ischemia/Reperfusion Injury Rat Model Through the E2F1/EZH2/TIMP2 Regulatory Axis.Molecular neurobiology · 2022Article
- Gastric cancer: An epigenetic view.World journal of gastrointestinal oncology · 2022Review
- SUMOylation inhibition enhances dexamethasone sensitivity in multiple myeloma.Journal of experimental & clinical cancer research : CR · 2022Article
- SUMOylation and NEDDylation in Primary and Metastatic Cancers to Bone.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Elevated expression of EZH2, the enzymatic subunit of polycomb repressive complex 2 (PRC2), often occurs in cancer. EZH2 expression results in the silencing of genes that suppress tumor formation and metastasis through trimethylation of histone H3 at lysine 27 (H3K27me3) at their promoters. However, inhibitors of EZH2 enzymatic activity have not shown the expected efficacy against cancer in clinical trials, suggesting a need for other strategies to address EZH2 overexpression. Here, we show that SUMOylation, a posttranslational modification characterized by covalent attachment of small ubiquitin-like modifier (SUMO) proteins to a lysine (Lys) residue on target proteins, enhances EZH2 transcription. Either knockdown of the SUMO-activating enzyme SAE2 or pharmacologic inhibition of SUMOylation resulted in decreased levels of EZH2 mRNA and protein as well as reduced H3K27me3 levels. SUMOylation regulated EZH2 expression by enhancing binding of the E2F1 transcriptional activator to the EZH2 promoter. Inhibition of SUMOylation not only resulted in reduced EZH2 mRNA and protein levels but also increased expression of genes silenced by EZH2, such as E-cadherin, which suppresses epithelial-mesenchymal transition and metastasis. In more than 6,500 patient tumor samples across different cancer types, expression of UBA2 and EZH2 was positively correlated. Taken together, our findings suggest that inhibition of SUMOylation may serve as a potential strategy to address EZH2 overexpression and improve current cancer therapeutic approaches. SIGNIFICANCE: These findings provide important biological insights into the mechanism of EZH2 overexpression in cancers and suggest that inhibiting SUMOylation may improve current cancer therapeutic approaches.
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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.