ArticleInternational journal of molecular sciences2016
Aberrant JAK/STAT Signaling Suppresses TFF1 and TFF2 through Epigenetic Silencing of GATA6 in Gastric Cancer.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- miR-196b inhibits tumor proliferation and metastasis by targeting GATA6 in endometrial cancer.Biology direct · 2026Article
- Loss of glomerular aldolase B in diabetic nephropathy promotes renal fibrosis via activating Akt/GSK/β-catenin axis.Journal of advanced research · 2025Article
- Different Master Regulators Define Proximal and Distal Gastric Cancer: Insights into Prognosis and Opportunities for Targeted Therapy.Current oncology (Toronto, Ont.) · 2025Article
- Metabolic Reprogramming in Cancer Cells: Emerging Molecular Mechanisms and Novel Therapeutic Approaches.Pharmaceutics · 2022Review
- MicroRNA Regulation of T-Cell Exhaustion in Cutaneous T Cell Lymphoma.The Journal of investigative dermatology · 2022Article
- Inhibitors Targeting Multiple Janus Kinases FromFrontiers in chemistry · 2022Article
- LINGO3 regulates mucosal tissue regeneration and promotes TFF2 dependent recovery from colitis.Scandinavian journal of gastroenterology · 2021Article
- Diagnostic and therapeutic potencies of miR-18a-5p in mixed-type gastric adenocarcinoma.Journal of cellular biochemistry · 2021Article
- Efficacy of niclosamide on the intra-abdominal inflammatory environment in endometriosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Methylomic analysis identifies C11orf87 as a novel epigenetic biomarker for GI cancers.PloS one · 2021Article
- Epigenetic Silencing of STAT3-Targeted miR-193a, by Constitutive Activation of JAK/STAT Signaling, Leads to Tumor Progression Through Overexpression of YWHAZ in Gastric Cancer.Frontiers in oncology · 2021Article
- HDAC1 and 2 regulate endothelial VCAM-1 expression and atherogenesis by suppressing methylation of theTheranostics · 2021Article
- Metabolic Reprogramming in Gastric Cancer: Trojan Horse Effect.Frontiers in oncology · 2021Review
- Integrative analysis of ceRNA network and DNA methylation associated with gene expression in malignant pheochromocytomas: a study based on The Cancer Genome Atlas.Translational andrology and urology · 2020Article
- Targeting the JAK/STAT pathway in solid tumors.Journal of cancer metastasis and treatment · 2020Article
- Activation of STAT3 signaling is mediated by TFF1 silencing in gastric neoplasia.Nature communications · 2019Article
- Novel Gastric Cancer Stem Cell-Related Marker LINGO2 Is Associated with Cancer Cell Phenotype and Patient Outcome.International journal of molecular sciences · 2019Article
- Article
- EGFR-targeted photodynamic therapy by curcumin-encapsulated chitosan/TPP nanoparticles.International journal of nanomedicine · 2018Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling is crucial to the development of gastric cancer. In this study, we examined the role of STAT3 in the expression and methylation of its targets in gastric cancer patients. Results from RNA sequencing identified an inverse correlation between the expression of STAT3 and GATA6 in 23 pairs of gastric cancer patient samples. We discovered that the expression of GATA6 is epigenetically silenced through promoter methylation in gastric cancer cell lines. Interestingly, the inhibition of STAT3 using a novel STAT3 inhibitor restored the expression of GATA6 and its targets, trefoil factors 1 and 2 (TFF1/2). Moreover, disruption of STAT3 binding to GATA6 promoter by small hairpin RNA restored GATA6 expression in AGS cells. A clinically significant correlation was also observed between the expression of GATA6 and TFF1/2 among tissue samples from 60 gastric cancer patients. Finally, bisulfite pyrosequencing revealed GATA6 methylation in 65% (39/60) of the patients, and those with higher GATA6 methylation tended to have shorter overall survival. In conclusion, we demonstrated that aberrant JAK/STAT signaling suppresses TFF1/2 partially through the epigenetic silencing of GATA6. Therapeutic intervention of STAT3 in reversing the epigenetic status of GATA6 could benefit the treatment of gastric cancer and is worthy of further investigation.
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