ArticleCancer management and research2021
TGF-β-MTA1-SMAD7-SMAD3-SOX4-EZH2 Signaling Axis Promotes Viability, Migration, Invasion and EMT of Hepatocellular Carcinoma Cells.
Article in Cancer management and research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- SINEUP-mediated enhancement of HNF4α improves metabolic function in Huh7-based bioengineered hepatic microtissues.Journal of liver cancer · 2026Article
- Post-transcriptional activation of TGF-β signaling via SMAD mRNA stabilization by EIF4A3 promotes EMT and metastasis in gastric cancer.Cell biology and toxicology · 2026Article
- Identification of metastasis-associated protein 1 (MTA1) as a new molecular marker for canine urothelial carcinoma.Frontiers in veterinary science · 2025Article
- Article
- EZH2 K63-polyubiquitination affecting migration in extranodal natural killer/T-cell lymphoma.Clinical epigenetics · 2023Article
- EMT-related gene risk model establishment for prognosis and drug treatment efficiency prediction in hepatocellular carcinoma.Scientific reports · 2023Article
- Liposomal DQ in Combination with Copper Inhibits ARID1A Mutant Ovarian Cancer Growth.Biomolecules · 2023Article
- Rebalancing SMAD7/SMAD3 Signaling Reduces Adhesion Formation during Flexor Tendon Healing.Journal of microbiology and biotechnology · 2023Article
- Identification of Prognosis-Related Oxidative Stress Model with Immunosuppression in HCC.Biomedicines · 2023Article
- FXR1 promotes proliferation, invasion and migration of hepatocellular carcinomaOncology letters · 2023Article
- Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies.Frontiers in pharmacology · 2023Review
- Identification and validation of a novel cuproptosis-related genes signature associated with prognosis, clinical implications and immunotherapy of hepatocellular carcinoma.Frontiers in pharmacology · 2023Article
- Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma.World journal of gastroenterology · 2022Review
- Comprehensive competitive endogenous RNA network analysis revealsIranian journal of basic medical sciences · 2022Article
- The Role of Long Non-Coding RNA and microRNA Networks in Hepatocellular Carcinoma and Its Tumor Microenvironment.International journal of molecular sciences · 2021Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionEnhancer of zeste homolog 2 (EZH2) is implicated in hepatocellular carcinoma (HCC), but whether transforming growth factor-β (TGF-β)-metastasis associated 1 (MTA1)-SMAD7-SMAD3-SRY-Box Transcription Factor 4 (SOX4)-EZH2 signaling axis, in which EZH2 participates, is also involved in HCC remained unknown.
methodsData on EZH2 expression in liver hepatocellular carcinoma (LIHC) and its relation with prognosis of HCC patients were predicted and analyzed using online databases. Following transfection with or without TGF-β1, HCC cell viability, migration and invasion were determined with MTT, Scratch and Transwell assays. Relative expressions of epithelial-to-mesenchymal transition (EMT)-related factors (N-Cadherin, Vimentin, and E-Cadherin) and TGF-β-MTA1-SMAD7-SMAD3-SOX4-EZH2 signaling axis factors (TGF-β, MTA1, SMAD7, phosphorylated-SMAD3, SOX4 and EZH2) were calculated via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot.
resultsEZH2 was upregulated in HCC, which was related to poor prognosis. Silencing EZH2 suppressed EZH2 expression and HCC cell viability, migration, and invasion, and increased E-Cadherin expression yet decreased N-Cadherin and Vimentin expression, whereas EZH2 overexpression did conversely. Also, silencing EZH2 reversed the effects of TGF-β1 on promoting viability, migration, and invasion, as well as N-Cadherin and Vimentin expressions, yet suppressing E-Cadherin expression in HCC cells. In addition, TGF-β1 promoted TGF-β, MTA1, SOX4 and EZH2 expressions and p-SMAD3/SMAD3 ratio yet suppressed SMAD7, whereas silencing EZH2 solely reversed the effects of TGF-β1 on EZH2 expression in HCC cells.
conclusionThe present study provides a theoretical basis for TGF-β-MTA1-SMAD7-SMAD3-SOX4-EZH2 signaling cascade in viability, migration, invasion, and EMT of HCC cells. Inhibiting these signals may represent a therapeutic pathway for the treatment of metastatic HCC.
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