Long non-coding RNAs as determinants of cell fate in gastric cancer: Molecular mechanisms governing survival and programmed cell death.

Abstract

Long non-coding RNAs (lncRNAs) are now recognized as important modulators of gene expression acting at the transcriptional, post-transcriptional, and epigenetic levels. A growing number of studies suggest that abnormal lncRNA expression plays a critical role in gastric carcinogenesis by controlling cellular functions such as proliferation, cell-cycle progression, apoptosis, autophagy, and other forms of regulated cell death. This review discusses the molecular pathways through which lncRNAs contribute to gastric carcinogenesis, particularly by regulating cell fate, proliferation, and apoptosis. We also summarize the functions of major oncogenic and tumor-suppressive lncRNAs, including HOTAIR, MALAT1, H19, GAS5, DINO, PANDAR and their associations with PI3K/AKT, Wnt/β-catenin, MAPK, JAK/STAT, and p53 signaling. Associations among lncRNAs, ferroptosis, treatment response, and tumor progression are also discussed. Overall, available evidence identifies lncRNAs as key mediators of gastric carcinogenesis and as potential diagnostic biomarkers and therapeutic targets.