Uncovering the Role of Small and Intermediate-Length Non-Coding RNAs in Glioma Pathogenesis and Prognosis

Gliomas are the most prevalent and aggressive primary tumors of the central nervous system (CNS), with glioblastoma demonstrating particularly poor survival rates despite multimodal treatment approaches. The extensive molecular heterogeneity and resistance to conventional therapies highlight the urgent need for novel biomarkers and therapeutic targets. Non-coding RNAs (ncRNAs), transcripts that do not encode proteins, have emerged as crucial regulators of gene expression and cellular homeostasis in both normal and malignant contexts. Their dysregulation contributes to key oncogenic processes, including uncontrolled proliferation, apoptosis, evasion, invasion, and therapeutic resistance. Small and intermediate-sized are strong candidates for biomarkers due to their high abundance and relative stability. Previous reviews on ncRNAs highlight the numerous roles of microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in gliomas. Here, we focus specifically on small and intermediate-length non-coding RNAs, including transfer RNAs (tRNAs) and tRNA-derived fragments (tRFs or tsRNAs), small nucleolar RNAs (snoRNAs), vault RNAs (vRNAs or vtRNAs), small nuclear RNAs (snRNAs) and mitochondrial tRNAs (mt-tRNAs). Recent studies suggest that these various non-coding RNAs participate in diverse aspects of glioma biology, including regulation of gene expression and modulation of metabolic and immune pathways, and correlate with tumor grade and molecular subtype. In this review, we summarize current evidence regarding the expression profiles and functional roles of small and intermediate-length non-coding RNAs in glioma tumorigenesis, progression, and therapeutic response. The differential expression of many of these ncRNAs in gliomas implies their involvement in both tumor-suppressive and oncogenic processes. A deeper understanding of these molecules may provide valuable insights into glioma biology and reveal novel biomarkers for diagnosis, prognosis, and treatment.