ArticleBMC biology2022
SMYD3 associates with the NuRD (MTA1/2) complex to regulate transcription and promote proliferation and invasiveness in hepatocellular carcinoma cells.
Article in BMC biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- R‑loops in hepatocellular carcinoma: Bridging genomic instability and therapeutic opportunity (Review).Molecular medicine reports · 2026Review
- SMYD3-CDCP1 Axis Drives EMT and CAF Activation in Colorectal Cancer and Is Targetable for Oxaliplatin Sensitization.Biomedicines · 2025Article
- Loss of histone methyltransferase Smyd3 triggers WAT browning and adaptive thermogenesis via enhancing PPARγ expression in a H4K20me3-dependent manner.Journal of translational medicine · 2025Article
- SMYD3 drives cell cycle and epithelial-mesenchymal transition pathways through dual gene transcriptional repression and activation in HPV-negative head and neck cancer.Scientific reports · 2025Article
- Whole-genome sequencing identifies novel genes for autism in Chinese trios.Science China. Life sciences · 2024Article
- SMYD family in cancer: epigenetic regulation and molecular mechanisms of cancer proliferation, metastasis, and drug resistance.Experimental & molecular medicine · 2024Review
- MLL4 Regulates the Progression of Non-Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis.Cancer research and treatment · 2023Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSMYD3, a member of the SET and MYND domain-containing (SMYD) family, is a histone methyltransferase (HMT) and transcription factor that plays an important role in transcriptional regulation in human carcinogenesis.
resultsUsing affinity purification and mass spectrometry assays to identify SMYD3-associated proteins in hepatocellular carcinoma (HCC) cells, we found several previously undiscovered SMYD3-interacting proteins, including the NuRD (MTA1/2) complex, the METTL family, and the CRL4B complex. Transcriptomic analysis of the consequences of knocking down SMYD3, MTA1, or MTA2 in HCC cells showed that SMYD3/NuRD complex targets a cohort of genes, some of which are critically involved in cell growth and migration. qChIP analyses showed that SMYD3 knockdown led to a significant reduction in the binding of MTA1 or MTA2 to the promoters of IGFBP4 and led to a significant decrease in H4K20me3 and a marked increase in H4Ac at the IGFBP4 promoter. In addition, we demonstrated that SMYD3 promotes cell proliferation, invasion, and tumorigenesis in vivo and in vitro and found that its expression is markedly upregulated in human liver cancer. Knockdown of MTA1 or MTA2 had the same effect as knockdown of SMYD3 on proliferation and invasion of hepatocellular carcinoma cells. Catalytic mutant SMYD3 could not rescue the phenotypic effects caused by knockdown of SMYD3. Inhibitors of SMYD3 effectively inhibited the proliferation and invasiveness of HCC cells.
conclusionsThese findings revealed that SMYD3 could transcriptionally repress a cohort of target genes expression by associating with the NuRD (MTA1/2) complex, thereby promoting the proliferation and invasiveness of HCC cells. Our results support the case for pursuing SMYD3 as a practical prognostic marker or therapeutic target against HCC.
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