# Glycosylated RNAs: discovery and implications in cancer biology

**Authors:** Shuai Tang, Ximo Wang, Fangmin Chen, Benyi Li

PMC · DOI: 10.3389/fonc.2026.1719799 · Frontiers in Oncology · 2026-02-04

## TL;DR

Glycosylated RNAs, a new class of biomolecules, are being studied for their roles in cancer biology and potential as biomarkers or therapeutic targets.

## Contribution

This paper reviews the discovery of glycosylated RNAs and their emerging roles in cancer, emphasizing detection methods and potential clinical applications.

## Key findings

- Glycosylated RNAs are found in multiple cellular compartments and may influence intercellular communication and immune regulation.
- Recent detection techniques link glycoRNA patterns to tumor aggressiveness and immune checkpoint regulation.
- The paper highlights the need for further research into glycoRNA biosynthesis and structural diversity for precision oncology.

## Abstract

Glycosylated RNAs (glycoRNAs) are a newly discovered class of biomolecules that challenge the long-standing paradigm that glycosylation occurs exclusively on proteins and lipids. Early studies indicate that glycoRNAs are broadly distributed across cell types and can be detected at the cell surface as well as in other cellular compartments. Emerging evidence suggests that glycoRNAs may participate in processes such as intercellular communication and immune regulation, but their context-dependent functions in physiology and disease, including cancer, are only beginning to be elucidated. Recent advances in detection techniques have enabled more comprehensive profiling of glycoRNAs and their associated cell-surface RNA-binding proteins, providing initial links between glycoRNA patterns, tumor aggressiveness, immune checkpoint regulation and extracellular vesicle–mediated signaling. However, many of these connections remain correlative or are inferred by analogy to protein and lipid glycosylation. In this review, we summarize current knowledge of glycoRNA biosynthesis, cell-surface display and detection methods, with a particular focus on emerging observations in cancer-related contexts. We also discuss the potential of glycoRNAs as biomarkers and therapeutic targets, while highlighting key unanswered questions regarding their biosynthetic pathways, structural diversity and mechanistic roles. Addressing these challenges with integrated omics and spatial approaches will be essential for defining glycoRNA biology and evaluating their feasibility as tools for precision oncology.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** NPM1 (nucleophosmin 1) [NCBI Gene 4869] {aka B23, NPM}, B4GALT1 (beta-1,4-galactosyltransferase 1) [NCBI Gene 2683] {aka B4GAL-T1, CDG2D, CLDLFIB, GGTB2, GT1, GTB}, ENO1 (enolase 1) [NCBI Gene 2023] {aka ENO1-IT1, ENO1L1, HEL-S-17, MPB1, NNE, PPH}, SSB (small RNA binding exonuclease protection factor La) [NCBI Gene 6741] {aka LARP3, La, La/SSB, SSB/La}, RO60 (Ro60, Y RNA binding protein) [NCBI Gene 6738] {aka RORNP, SSA2, TROVE2}, CDK11B (cyclin dependent kinase 11B) [NCBI Gene 984] {aka CDC2L1, CDK11, CDK11-p110, CDK11-p46, CDK11-p58, CLK-1}, sid-1 (Systemic RNA interference defective protein 1) [NCBI Gene 178900], MCF2L (MCF.2 cell line derived transforming sequence like) [NCBI Gene 23263] {aka ARHGEF14, DBS, OST}, STT3A (STT3 oligosaccharyltransferase complex catalytic subunit A) [NCBI Gene 3703] {aka CDG1WAD, CDG1WAR, ITM1, STT3-A, TMC}, TAT (tyrosine aminotransferase) [NCBI Gene 6898], AFP (alpha fetoprotein) [NCBI Gene 174] {aka AFPD, FETA, HPAFP}, NPEPPS (aminopeptidase puromycin sensitive) [NCBI Gene 9520] {aka AAP-S, MP100, PSA}, DDX21 (DExD-box helicase 21) [NCBI Gene 9188] {aka GUA, GURDB, II/Gu, RH, RH II/Gu, RH-II/GU}, SIGLEC5 (sialic acid binding Ig like lectin 5) [NCBI Gene 8778] {aka CD170, CD33L2, OB-BP2, OBBP2, SIGLEC-5}, SLC35A1 (solute carrier family 35 member A1) [NCBI Gene 10559] {aka CDG2F, CMPST, CST, hCST}, ELAVL1 (ELAV like RNA binding protein 1) [NCBI Gene 1994] {aka ELAV1, HUR, Hua, MelG}, SNRNP200 (small nuclear ribonucleoprotein U5 subunit 200) [NCBI Gene 23020] {aka ASCC3L1, BRR2, HELIC2, RP33, U5-200KD}, NUCLEOLIN (nucleolin multifunctional protein) [NCBI Gene 4691] {aka C23, NCL, Nsr1}, DTWD2 (DTW motif tRNA-uridine aminocarboxypropyltransferase 2) [NCBI Gene 285605], YBX1 (Y-box binding protein 1) [NCBI Gene 4904] {aka BP-8, CBF-A, CSDA2, CSDB, DBPB, EFI-A}, CMAS (cytidine monophosphate N-acetylneuraminic acid synthetase) [NCBI Gene 55907] {aka CSS}, LINC00339 (long intergenic non-protein coding RNA 339) [NCBI Gene 29092] {aka HSPC157, NCRNA00339}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, HNRNPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1) [NCBI Gene 3181] {aka HNRNPA2, HNRNPB1, HNRPA2, HNRPA2B1, HNRPB1, IBMPFD2}
- **Diseases:** hepatocellular carcinoma (MESH:D006528), breast cancer (MESH:D001943), metastasis (MESH:D009362), colorectal cancer (MESH:D015179), leukemic (MESH:D007938), precancerous lesions (MESH:D011230), hematological malignancies (MESH:D019337), AML (MESH:D015470), gastric cancer (MESH:D013274), autoimmune diseases (MESH:D001327), tumorigenesis (MESH:D063646), Tumor (MESH:D009369), prostate cancer (MESH:D011471), inflammation (MESH:D007249)
- **Chemicals:** gemcitabine (MESH:D000093542), sphingolipid (MESH:D013107), fucose (MESH:D005643), lipid (MESH:D008055), sialic acids (MESH:D012794), heparan-sulfate (MESH:D006497), GalNAc (-), oxime (MESH:D010091), copper (MESH:D003300), N-acetylgalactosamine (MESH:D000116), glycolipid (MESH:D006017), biotin (MESH:D001710), Aldehyde (MESH:D000447), cholesterol (MESH:D002784), Tn (MESH:C009497), Tunicamycin (MESH:D014415), azide (MESH:D001386), glycan (MESH:D011134), monosaccharide (MESH:D009005), sialic acid (MESH:D019158), Ac4ManNAz (MESH:C000622612), Periodate (MESH:C009288)
- **Species:** Homo sapiens (human, species) [taxon 9606], C. elegans [taxon 328850], Human immunodeficiency virus 1 (no rank) [taxon 11676], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006), K562 — Homo sapiens (Human), Blast phase chronic myelogenous leukemia, BCR-ABL1 positive, Cancer cell line (CVCL_0004), HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063)

## Full text

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## Figures

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## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12913191/full.md

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Source: https://tomesphere.com/paper/PMC12913191