Extracellular Y RNA fragments in gastrointestinal cancer and a proposed role for YBX1 in macrophage responses
- 1Department of Oncology, Zibo Central Hospital, Zibo
Abstract
Tumor-derived extracellular vesicles (EVs) can alter macrophage responses, but the contribution of individual RNA cargoes remains difficult to establish. Y RNA-derived fragments are candidate mediators whose mechanisms after EV exposure have not been conclusively defined across physiological settings. This review examines reported EV-associated macrophage effects in gastrointestinal (GI) cancer, Y RNA studies from other diseases, and a possible role for RNA modifications and RNA-binding proteins. Separate experimental systems link YBX1 protein methylation to fragment sorting, damage-associated Y3 RNA methylation to YBX1 binding and PARP1 activity, and extracellular hY4 to monocyte responses through TLR7. These observations do not establish a continuous pathway in GI cancer. We propose that a sequence-defined Y RNA fragment could reach recipient macrophages, bind YBX1 in an m5C-sensitive manner, and alter a measurable molecular process before changing macrophage function. Whether this occurs, whether RNA methylation precedes or follows transfer, and whether the response supports tumor growth remain unresolved. A cardiac study using a synthetic Y RNA fragment reported reduced inflammatory-cell recruitment, illustrating that RNA responses can differ with disease and treatment context. The review distinguishes vesicle uptake from functional RNA delivery and considers endosomal sensing, other EV cargoes, and donor-cell effects as alternative explanations. Testing this hypothesis will require demonstrating functional delivery of a defined Y RNA fragment and YBX1-dependent macrophage effects in the same GI cancer model.
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BibTeX
@article{wang2026extracellular,
title = {{Extracellular Y RNA fragments in gastrointestinal cancer and a proposed role for YBX1 in macrophage responses}},
author = {Xitan Wang and Fuli Wang and Wei Tian},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1902611},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1902611/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Extracellular Y RNA fragments in gastrointestinal cancer and a proposed role for YBX1 in macrophage responses
AU - Xitan Wang
AU - Fuli Wang
AU - Wei Tian
PY - 2026
DA - 2026/10/20
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1902611
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1902611/full
AB - Tumor-derived extracellular vesicles (EVs) can alter macrophage responses, but the contribution of individual RNA cargoes remains difficult to establish. Y RNA-derived fragments are candidate mediators whose mechanisms after EV exposure have not been conclusively defined across physiological settings. This review examines reported EV-associated macrophage effects in gastrointestinal (GI) cancer, Y RNA studies from other diseases, and a possible role for RNA modifications and RNA-binding proteins. Separate experimental systems link YBX1 protein methylation to fragment sorting, damage-associated Y3 RNA methylation to YBX1 binding and PARP1 activity, and extracellular hY4 to monocyte responses through TLR7. These observations do not establish a continuous pathway in GI cancer. We propose that a sequence-defined Y RNA fragment could reach recipient macrophages, bind YBX1 in an m5C-sensitive manner, and alter a measurable molecular process before changing macrophage function. Whether this occurs, whether RNA methylation precedes or follows transfer, and whether the response supports tumor growth remain unresolved. A cardiac study using a synthetic Y RNA fragment reported reduced inflammatory-cell recruitment, illustrating that RNA responses can differ with disease and treatment context. The review distinguishes vesicle uptake from functional RNA delivery and considers endosomal sensing, other EV cargoes, and donor-cell effects as alternative explanations. Testing this hypothesis will require demonstrating functional delivery of a defined Y RNA fragment and YBX1-dependent macrophage effects in the same GI cancer model.
SN - 1664-3224
ER -