ArticleJournal of translational medicine2025
Epicatechin attenuates the stemness of liver cancer stem cells and tumorigenesis through DNA methylation-mediated inactivation of GINS1/HRAS.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Epicatechin suppresses cancer stem-like cell phenotype and radioresistance in non-small cell lung cancer via targeting CXCL8.Biology direct · 2026Article
- Dietary polyphenols and hepatocellular carcinoma: protective mechanisms, challenges, and future directions.Discover oncology · 2026Review
- Crosstalk BetweenCancers · 2026Review
- Stemness CD24 activation promotes hepatocellular carcinoma progressionWorld journal of gastroenterology · 2026Article
- Epigenetic regulation in cancer chemoresistance and combined therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
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7 authors.
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Abstract
backgroundThe limited therapeutic options for hepatocellular carcinoma (HCC) are primarily attributed to the presence of liver cancer stem cells (LCSCs). Epicatechin (EC) is known to exert therapeutic effects on cancer. Go-ichi-ni-san complex subunit 1 (GINS1) is an oncogene associated with HCC and represents a potential target for cancer therapy. In this study, we investigated the molecular mechanisms of EC by which modulates DNA methylation and inhibits GINS1, thereby affecting LCSCs and HCC malignancy.
methodsCancer Genome Atlas (TCGA) database was employed to analyze the differences in GINS1 and HRAS expression levels between HCC tissues and normal tissues. The effect of EC on GINS1 and HRAS expression was measured by qPCR and western blotting. Sphere formation assay, CCK-8 assays and transwell assays were used to evaluate the malignant behaviors of HCC cells in vitro. Stemness markers (Nanog, OCT4 and SOX2) were analyzed by western blotting. Methylation-specific PCR was conducted to assess DNA methylation level on GINS1 promoter. The correlation between GINS1 and HRAS in HCC was evaluated using spearman's rank correlation analysis and confirmed through co-immunoprecipitation and GST pulldown assay. Additionally, xenograft tumor models based on HCC cells were conducted to investigate the anti-tumor effects of EC in vivo.
resultsElevated expression of GINS1 was observed in HCC cells and LCSCs. Silencing GINS1 repressed LCSC phenotype, diminished the malignant behaviors of HCC cells and inhibited tumorigenesis. We further found EC attenuated LCSC phenotype and tumorigenesis by downregulating GINS1 expression. Mechanistically, administration of EC enhanced DNA methylation on the GINS1 promoter, leading to a subsequent reduction in GINS1 levels. Additionally, we found that GINS1 could interact with HRAS and activate HRAS, thereby inducing LCSC phenotype and promoting tumorigenesis. Overexpression of HRAS partially counteracted the inhibitory effects on LCSC phenotype induction and tumorigenesis mediated by GINS1 silencing or EC administration.
conclusionTaken together, our findings suggest an important role of the EC/DNA methylation/GINS1/HRAS pathway in regulating LCSCs properties, suggesting potential therapeutic targets for HCC.
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