ArticleEpigenetics2023
DNMT1 expression partially dictates 5-Azacytidine sensitivity and correlates with RAS/MEK/ERK activity in gastric cancer cells.
Article in Epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- From Food Contaminant to Therapeutic Target: Identification of KCNE2 and 5-Azacytidine for Gastric Cancer via Multi-Omics, Machine Learning, and In Vitro Validation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Review
- Multiscale characterization of an inflammatory macrophage state associated with an air pollutant-prioritized prognostic signature in gastric cancer.Frontiers in immunology · 2026Article
- Epigenetics of glaucoma in the trabecular meshwork.Clinical epigenetics · 2025Review
- Restoration of Autophagy and Apoptosis in Myelodysplastic Syndromes: The Effect of Azacitidine in Disease Pathogenesis.Current issues in molecular biology · 2025Article
- DNMT1/MTTP axis promotes gastritis progression duringEpigenomics · 2025Article
- Platinum drugs upregulate CXCR4 and PD-L1 expression via ROS-dependent pathways, with implications for novel combined treatment in gastric cancer.The journal of pathology. Clinical research · 2025Article
- Identification and Validation of a Cancer-Testis Antigen-Related Signature to Predict the Prognosis in Stomach Adenocarcinoma.Journal of Cancer · 2024Article
- Impact of KRAS mutation on the tumor microenvironment in colorectal cancer.International journal of biological sciences · 2024Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Though DNMTs inhibitors were widely used in myelodysplastic syndrome and leukaemia, their application in solid tumours has been limited by low response rate and lack of optimal combination strategies. In gastric cancer (GC), the therapeutic implication of KRAS mutation or MEK/ERK activation for combinational use of DNMTs inhibitors with MEK/ERK inhibitors remains elusive. In this study, stable knockdown of DNMT1 expression by lentiviral transfection led to decreased sensitivity of GC cells to 5-Azacytidine. KRAS knockdown in KRAS mutant GC cells or the MEK/ERK activation by EGF stimulation in GC cells increased DNMT1 expression, while inhibition of MEK/ERK activity by Selumetinib led to decreased DNMT1 expression. 5-Azacytidine treatment, which led to dramatic decline of DNMTs protein levels and increased activity of MEK/ERK pathway, altered the activity of MEK/ERK inhibitor Selumetinib on GC cells. Both RAS-dependent gene expression signature and expression levels of multiple MEK/ERK-dependent genes were correlated with DNMT1 expression in TCGA stomach cancer samples. In conclusion, DNMT1 expression partially dictates 5-Azacytidine sensitivity and correlates with RAS/MEK/ERK activity in GC cells. Combining DNMTs inhibitor with MEK/ERK inhibitor might be a promising strategy for patients with GC.[Figure: see text].
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