# Signatures of micropeptides encoded by lncRNAs in cancer progression and metastasis

Article · Zok S, Linial M

- Archive id: doi:10.1038/s41416-026-03556-1
- Published: 2026-07-27
- Venue: British journal of cancer
- DOI: https://doi.org/10.1038/s41416-026-03556-1
- PMID: 42509464
- PMCID: PMC13675225
- Citations: 1
- Source URL: https://doi.org/10.1038/s41416-026-03556-1
- PDF: https://europepmc.org/articles/PMC13675225/pdf
- Provenance: europepmc

## Abstract

Background Long non-coding RNAs (lncRNAs) regulate gene expression, chromatin organization, and cellular signaling. Although traditionally considered non-coding, 21% of the ~190,000 annotated lncRNA transcripts contain poorly characterized open reading frames with unknown function. Methods We systematically identified lncRNAs encoding micropeptides (MPs) using integrated computational and experimental evidence. Expression profiles across 17 cancer types from The Cancer Genome Atlas (TCGA) were analyzed to identify cancer-associated and transitional lncRNAs (Tr-lncRNAs). Structural modeling using AlphaFold was further applied to predict folding. Results We identified 478 lncRNA genes encoding 1782 MPs (10-100 amino acids). These MPs exhibit distinct amino acid and dipeptide compositions and are enriched for specific 4-mer motifs compared with canonical proteins. A subset of lncRNAs, including TNN-AS1, PVT1, XIST, and SNHG family members, encode multiple MPs. Analysis across cancer stages identified 2399 Tr-lncRNAs, most of them were cancer type and stage specific. Among these, 314 highly confident MPs from 72 Tr-lncRNAs were further analyzed. Pan-cancer analysis suggested MP-like functions for Tr-lncRNAs such as LINC01234, HAND2-AS1, XIST, UCA1, and HOXA11-AS. While most MPs are predicted to be intrinsically disordered, 3D structural modeling revealed several MPs with stable folds, including ubiquitin-like and RNase H-like structures. Conclusions Tr-lncRNA-derived MPs represent a previously underexplored class of potentially functional molecules associated with cancer clinical annotation and may serve as biomarkers for disease progression.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [AI Protein Design & Structure Prediction](https://space-kitty.com/topics/protein-design)

---
Space Kitty Archive · https://space-kitty.com · API: https://space-kitty.com/api/v1 · MCP: https://space-kitty.com/mcp · Premium: $0.20/request via x402 (Base Sepolia (testnet)). Metadata: arXiv (CC0), OpenAlex (CC0), Europe PMC (CC BY/CC0 works), ClinicalTrials.gov.