Non-coding RNAs-mediated regulation of the MAPK pathway in gastric cancer: translational perspectives

In recent years, non-coding RNAs (ncRNAs) have been acknowledged as master regulators of various cellular behaviors, and their dysregulation contributes to the development, progression, and therapeutic resistance of various cancers, including gastric cancer (GC). The mitogen-activated protein kinases (MAPKs) signaling pathways are frequently dysregulated in GC, leading to tumor initiation, progression, cell death resistance, metastasis, and therapeutic resistance. Emerging evidence supports the critical role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long ncRNAs (lncRNAs), in the regulation of MAPK pathways. These molecules can act as oncogenes or tumor suppressors by affecting components of the MAPK pathway or regulating their upstream regulators/downstream effectors. MAPK-regulating ncRNAs can drive various behaviors of malignant cells, including tumor growth and progression, angiogenesis, metastasis, immune evasion, and drug resistance. Understanding the regulatory network of MAPK-related ncRNAs can help develop novel biomarkers for diagnosis, predict prognosis, and stratify patients before treatment. Moreover, MAPK-regulating ncRNAs can serve as potential therapeutic targets in GC. In this review, we present an overview of current insights into ncRNA-mediated regulation of the MAPK pathway in GC, emphasizing the clinical relevance of these molecules. Moreover, the paths and challenges of the clinical use of MAPK-regulating ncRNAs as diagnostic/predictive biomarkers and therapeutic targets are comprehensively discussed. By elucidating the mechanistic roles of MAPK-regulating ncRNAs in GC, this review provides valuable insights into novel molecular biomarkers and innovative ncRNA-based therapies in GC management.