# Regulatory Mechanisms and Functional Roles of Readthrough Transcripts in Tumorigenesis

**Authors:** Alexander Modestov, Galina Zakharova, Elena Poddubskaya, Anton Buzdin

PMC · DOI: 10.3390/ijms26209975 · International Journal of Molecular Sciences · 2025-10-14

## TL;DR

This paper explores how extended gene transcripts, called readthrough transcripts, may act as cancer biomarkers and therapeutic targets.

## Contribution

The study investigates the functional roles and regulatory mechanisms of readthrough transcripts in tumor development.

## Key findings

- Readthrough transcripts can regulate gene expression and serve as prognostic markers in various cancers.
- These transcripts may produce novel proteins and overlap with neighboring genes through cis-splicing.
- The research identifies potential tumor-specific variants for use in diagnostics and drug development.

## Abstract

The search for novel tumor-specific markers and therapeutic targets is driving the development of more effective and personalized treatment strategies for cancer patients. This article focuses on investigating a promising new source of biomarkers—readthrough transcripts, or downstream-of-gene (DoG) transcripts. These transcripts are extended products of gene transcription that continue into intergenic regions and can overlap neighboring genes, sometimes giving rise to cis-splicing of adjacent gene (cis-SAGe) transcripts. Recent studies suggest that besides frequently being a “transcriptional noise”, DoG transcripts can perform regulatory functions, serve as a source of novel protein products, and act as prognostic markers of patient survival across various cancers. This article aims to investigate the regulatory mechanisms and functional significance of readthrough transcripts in tumors, to identify currently known tumor-specific variants with potential utility as cancer biomarkers or therapeutic targets, and to evaluate the most suitable approaches for their detection. The knowledge gained through this research may provide a foundation for the development of diagnostic test systems and the design of new anticancer drugs.

## Linked entities

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

## Full-text entities

- **Diseases:** cancer (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12564374/full.md

## References

89 references — full list in the complete paper: https://tomesphere.com/paper/PMC12564374/full.md

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Source: https://tomesphere.com/paper/PMC12564374