Background/aim: Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. MicroRNAs (miRNAs) are key regulators of tumorigenesis. This study investigated the role of the miR-192/215-early growth response protein 1 (EGR1) axis in GC and explored its therapeutic implications.
Materials and methods: Combinatorial molecular approaches including dual-luciferase reporter assays and western blot analyses were employed to authenticate EGR1 as a direct target of miR-192/215. Multi-modal data analysis incorporating The Cancer Genome Atlas datasets and our institutional cohort (n=56) was conducted to delineate EGR1 expression profiles across clinicopathological GC stages. Pharmacological modulation studies were implemented to characterize the dose- and time-dependent effects of epigallocatechin-3-gallate (EGCG) on the miR-192/215-EGR1 axis.
Results: EGR1 is a direct target of miR-192/215, with its expression negatively regulated by these miRNAs. Clinical analysis revealed significantly reduced EGR1 expression in tumors of early-stage GC (stage I) and cases with superficial invasion depth (T1) (p<0.05), suggesting a tumor-promoting role in the early stages of the disease. Higher EGR1 levels were associated with poorer overall survival, highlighting its potential as a prognostic biomarker (p<0.05). Furthermore, treatment of cells with EGCG transiently up-regulated miR-192/215 and down-regulated EGR1, highlighting its therapeutic potential.
Conclusion: This study highlights the miR-192/215-EGR1 axis as a critical regulator of GC progression and a promising therapeutic target. EGCG may serve as an adjunct therapy for GC. Future studies should focus on the regulatory mechanisms of EGR1, its interaction with the tumor microenvironment, and clinical validation of EGCG and other agents targeting this axis.
Keywords: EGR1; Gastric cancer; epigallocatechin gallate; miR-192; miR-215.
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