Biological roles and potential clinical values of snoRNAs in Cancer

Small nucleolar RNAs (snoRNAs), a class of intron-derived non-coding RNAs, primarily localize within the nucleolus and Cajal bodies. Based on conserved structural motifs and associated RNA modification functions, snoRNAs are classified into two main families: C/D box and H/ACA box. Conventionally, snoRNAs have been recognized for their canonical function in assembling small nucleolar ribonucleoproteins (snoRNPs) through interactions with core proteins. These complexes facilitate site-specific 2'-O-methylation and pseudouridylation of ribosomal RNAs (rRNAs) via sequence complementarity, thereby regulating rRNA biogenesis and function. Recent research has revealed a growing number of non-canonical mechanisms through which snoRNAs exert biological effects. These include direct interactions with proteins, the generation of functionally active snoRNA-derived RNAs (sdRNAs), and involvement in transcriptional regulation, epigenetic modification, translational control, and cellular signaling pathways that influence cell fate. Notably, increasing preclinical evidence indicates widespread dysregulation of snoRNAs in various malignancies. These molecules contribute to oncogenic processes by modulating cancer stemness, cell cycle progression, metabolic reprogramming, immune microenvironment remodeling, and promoting therapeutic resistance. These findings expand the functional understanding of snoRNAs and underscore their tissue-specific expression patterns and critical regulatory roles. Collectively, these attributes highlight the potential of snoRNAs as valuable diagnostic biomarkers and therapeutic targets in cancer management.