Core role of H19 LncRNA in gastric cancer: From tumor ecosystem reprogramming to precision therapy

Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. Owing to its insidious onset, most patients are diagnosed at advanced stages, marked by high recurrence, frequent metastasis, and multidrug resistance, resulting in poor outcomes. Optimizing therapeutic strategies therefore remains an urgent priority. Increasing evidence links GC initiation and progression to dysregulated expression of both coding and non-coding genes. Among them, long non-coding RNAs (lncRNAs) which recognized as pivotal regulators of gene expression have emerged as promising biomarkers and therapeutic targets. This review focuses on the lncRNA H19, highlighting its role as a central molecular hub in gastric tumor progression. H19 modulates the tumor microenvironment, promotes invasion and metastasis, reprograms cellular metabolism, and contributes to therapeutic resistance. By integrating molecular, cellular, and clinical perspectives, we provide a refined understanding of H19-driven gastric tumorigenesis and underscore its potential as a biomarker and therapeutic target. These insights offer new opportunities for early diagnosis, personalized treatment, and the development of RNA-targeted therapies for gastric cancer.