Role of glycosylated small noncoding RNAs in tumor: mechanism, function and clinical significance.

GlycoRNAs are a newly identified class of post‑transcriptionally modified small non‑coding RNAs that carry covalently attached N‑ and O‑linked glycans. This discovery challenges the conventional view that glycosylation is exclusive to proteins and lipids, and places RNA at the interface of glycobiology and immune recognition. Emerging evidence implicates glycoRNAs in tumor biology, where they function as cell‑surface ligands for Siglecs and P‑selectin, thereby modulating three interconnected processes: immune escape and immune regulation, intercellular communication and adhesion, and tumor metastasis and metabolic crosstalk. Recent technological advances-including single‑cell imaging (ARPLA), FRET‑based sEV analysis, and chemoenzymatic profiling-have enabled sensitive detection and revealed aberrant glycoRNA patterns across malignancies. Notably, tumor‑specific glycoRNA signatures correlate with immune checkpoint glycosylation (such as PD‑1/PD‑L1) and metabolic reprogramming. This review synthesizes current understanding of glycoRNA biosynthesis, structure, and function, with an emphasis on its emerging roles in the tumor microenvironment. We also outline the potential of RNA‑centric glycobiology for developing liquid biopsy biomarkers and mechanism‑informed immunotherapeutic strategies.