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Peer-reviewedCC BY 4.0Frontiers in Cell and Developmental Biology

Ribosomal RNA-derived fragments in cancer: molecular identity, cellular context, and functional evidence

  • Xianfang Shao1
  • Han Li2
  • Meiying Mu2
  • Zhenzhen Ma1
  1. 1Department of Critical Care Medicine, Zibo Central Hospital, Zibo, Shandong, China
  2. 2Department of Oncology, Zibo Central Hospital, Zibo, Shandong, China
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Abstract

Ribosomal RNA-derived fragments (rRFs), also termed rRNA-derived small RNAs (rsRNAs), occur in cells and biofluids, but their detection does not establish biological activity. This review systematically summarizes current research on rRF biogenesis, intracellular functions, extracellular localization and carriage, and clinical associations, while emphasizing that the detection of rRFs does not in itself establish biological function. Stress-associated cleavage, candidate-specific non-canonical processing, and extracellular ribosome fragmentation can each contribute to the observed repertoire. Functional cancer studies remain concentrated in a few candidates: depletion of a 28S-derived rRF3 affects H1299 cell phenotypes; rsRNA-28S inhibition increases PTGIS expression and taxane resistance in prostate-cancer cells; and synthetic gastric-cancer S2 and S7 mimics alter target reporters and protein abundance. These findings do not establish a common rRF pathway or therapeutic efficacy. Tissue and circulating signatures show diagnostic or prognostic associations, including a methylation-sensitive 28S fragment assay, but many cohorts are small and lack prospective external validation. Therapeutic development could test inhibition of a confirmed tumor-promoting fragment or replacement of a protective fragment, provided that endogenous function, selectivity over parental rRNA, delivery, and safety are established. Overall, rRFs show emerging biological and biomarker potential in cancer, but their clinical translation will require stronger mechanistic validation, prospective clinical evidence, and rigorous assessment of delivery and safety.

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Cite

BibTeXRIS
BibTeX
@article{shao2026ribosomal,
  title = {{Ribosomal RNA-derived fragments in cancer: molecular identity, cellular context, and functional evidence}},
  author = {Xianfang Shao and Han Li and Meiying Mu and Zhenzhen Ma},
  journal = {Frontiers in Cell and Developmental Biology},
  year = {2026},
  month = oct,
  doi = {10.3389/fcell.2026.1950076},
  url = {https://doi.org/10.3389/fcell.2026.1950076},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Ribosomal RNA-derived fragments in cancer: molecular identity, cellular context, and functional evidence
AU  - Xianfang Shao
AU  - Han Li
AU  - Meiying Mu
AU  - Zhenzhen Ma
PY  - 2026
DA  - 2026/10/22
JO  - Frontiers in Cell and Developmental Biology
DO  - 10.3389/fcell.2026.1950076
UR  - https://doi.org/10.3389/fcell.2026.1950076
AB  - Ribosomal RNA-derived fragments (rRFs), also termed rRNA-derived small RNAs (rsRNAs), occur in cells and biofluids, but their detection does not establish biological activity. This review systematically summarizes current research on rRF biogenesis, intracellular functions, extracellular localization and carriage, and clinical associations, while emphasizing that the detection of rRFs does not in itself establish biological function. Stress-associated cleavage, candidate-specific non-canonical processing, and extracellular ribosome fragmentation can each contribute to the observed repertoire. Functional cancer studies remain concentrated in a few candidates: depletion of a 28S-derived rRF3 affects H1299 cell phenotypes; rsRNA-28S inhibition increases PTGIS expression and taxane resistance in prostate-cancer cells; and synthetic gastric-cancer S2 and S7 mimics alter target reporters and protein abundance. These findings do not establish a common rRF pathway or therapeutic efficacy. Tissue and circulating signatures show diagnostic or prognostic associations, including a methylation-sensitive 28S fragment assay, but many cohorts are small and lack prospective external validation. Therapeutic development could test inhibition of a confirmed tumor-promoting fragment or replacement of a protective fragment, provided that endogenous function, selectivity over parental rRNA, delivery, and safety are established. Overall, rRFs show emerging biological and biomarker potential in cancer, but their clinical translation will require stronger mechanistic validation, prospective clinical evidence, and rigorous assessment of delivery and safety.
SN  - 2296-634X
ER  -