Small Nucleolar RNAs (snoRNAs) in Cancer: From Biogenesis to Clinical Potential.

SnoRNAs are regulatory RNAs that play indispensable roles in ribosomal RNA processing and translation. Their distinct structural conformations determine specific protein-binding partners, thereby mediating diverse epigenetic modifications. Most snoRNAs are transcribed from introns of snoRNA host genes (SNHGs). Processed snoRNAs can further yield piwi-interacting RNAs (piRNAs) and snoRNA-derived fragments (sdRNAs). These small RNA products are frequently dysregulated in tumors and exert significant oncogenic functions. In cancer, snoRNA dysregulation stems from DNA-level alterations such as chromosomal aberrations, base mutations, and gene silencing, as well as RNA-level disruptions including aberrant post-transcriptional modifications, degradation, and trafficking. Such dysregulated snoRNAs drive malignant hallmarks-sustained proliferation, invasion and metastasis, angiogenesis, metabolic reprogramming, immune evasion, senescence bypass, epigenetic remodeling, phenotypic plasticity, and microbiome-host crosstalk-through mechanisms spanning histone modifications, nucleic acid epitranscriptomics, and competitive endogenous RNA (ceRNA) networks. Consequently, tumor-associated snoRNAs detectable in body fluids represent promising non-invasive biomarkers for early cancer diagnosis and prognosis prediction. This review systematically summarizes snoRNA biogenesis pathways, elucidates mechanisms underlying their dysregulation in malignancies, summarizes the impact of aberrant snoRNAs on tumorigenesis and progression, and highlights clinically significant snoRNAs for diagnostic and therapeutic applications.