Alternative Splicing at the Crossroad of Inflammatory Bowel Diseases and Colitis-Associated Colon Cancer

Sep 23, 2026

The risk of developing colorectal cancer (CRC) is elevated in ulcerative colitis patients relative to the general population, driven by chronic inflammation that promotes tumour growth. This review characterizes colitis-associated colon cancer (CAC) and contrasts it with sporadic CRC, emphasizing key signalling pathways underpinning the transition. It highlights alternative splicing as an emerging mechanism through which inflammation alters transcript processing to increase CRC susceptibility. The review calls for expanded transcriptomic studies to define molecular drivers, support biomarker discovery, and enable therapies targeting splicing changes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Review

Simple Summary

Abstract

Keywords

1. Introduction

2. Cancer Risk in Patients with Inflammatory Bowel Disease

Review Alternative Splicing at the Crossroad of Inflammatory Bowel Diseases and Colitis-Associated Colon Cancer Paulo Matos 1,2, * and Peter Jordan 1,2, * Academic Editor: Matteo Landriscina Received: 4 December 2024 Revised: 6 January 2025 Accepted: 9 January 2025 Published: 11 January 2025 Citation: Matos, P.; Jordan, P. Alternative Splicing at the Crossroad of Inflammatory Bowel Diseases and Colitis-Associated Colon Cancer. Cancers 2025, 17, 219. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/cancers17020219](10.3390/cancers17020219) Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal 2 BioISI—Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal * [Correspondence: paulo.matos@insa.min-saude.pt](Correspondence: paulo.matos@insa.min-saude.pt) (P.M.); [peter.jordan@insa.min-saude.pt](peter.jordan@insa.min-saude.pt) (P.J.) Simple Summary: Patients with ulcerative colitis (UC) face a higher risk of developing colorectal cancer (CRC) due to chronic inflammation, a known promoter of tumour growth. Here, we review the molecular differences between colitis-associated cancer (CAC) and sporadic CRC, with a focus on “alternative splicing”, a mechanism by which the same gene can produce various protein forms. We explore how inflammation triggers changes in this process, increasing cancer risk for UC patients. The revised data emphasize that additional research into these molecular changes could help identify new biomarkers (molecules that indicate disease progression) and pave the way for innovative treatments targeting these alterations. Such advances would improve outcomes and quality of life for patients while contributing to cancer prevention and care. Abstract: The risk of developing colorectal cancer (CRC) is increased in ulcerative colitis patients compared to the general population. This increased risk results from the state of chronic inflammation, a well-known tumour-promoting condition. This review explores the pathologic and molecular characteristics of colitis-associated colon cancer (CAC), emphasizing the distinct features from sporadic CRC. We focus on the key signalling pathways involved in the transition to CAC, highlighting the emerging role of alternative splicing in these processes, namely on how inflammation-induced alternative splicing can significantly contribute to the increased CRC risk observed among UC patients. This review calls for more transcriptomic studies to elucidate the molecular mechanisms through which inflammation-induced alternative splicing drives CAC pathogenesis. Abetter understanding of these splicing events is crucial as they may reveal novel biomarkers for disease progression and have the potential to target changes in alternative splicing as a therapeutic strategy. Keywords: alternative splicing; colitis-associated cancer; interleukin; signalling pathway; splicing factor 1. Introduction Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders and the two main clinical presentations are ulcerative colitis (UC) or Crohn’s disease (CD) . Although incompletely understood, a dysregulated response of the mucosal immune system combined with alterations in the intestinal microbiome play a substantial role in the onset of the disease, particularly in genetically predisposed individuals [1,2] . A recent worldwide epidemiologic survey showed that IBD accounted for about 3.3 million cases in 1990 and 4.9 million cases in 2019, representing an increase in prevalence of almost 50%[3,4]. In Wes

FAQs

What increases colorectal cancer risk in ulcerative colitis patients?

Chronic inflammation promotes tumour growth, raising CRC risk compared with the general population.

What does the review focus on regarding colitis-associated colon cancer?

It examines pathologic and molecular characteristics of CAC and how it differs from sporadic CRC, with emphasis on key signalling pathways and alternative splicing.

Why is alternative splicing highlighted as important in this context?

Inflammation-induced alternative splicing can significantly contribute to the increased CRC risk in ulcerative colitis. The review argues for more transcriptomic studies to clarify the mechanisms and support biomarker and therapeutic development.

Sep 23, 2026

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