# Demystifying the Role of Histone Demethylases in Colorectal Cancer: Mechanisms and Therapeutic Opportunities

## TL;DR

This paper reviews how histone demethylases influence colorectal cancer progression and their potential as therapeutic targets.

## Contribution

The paper provides a comprehensive review of the mechanisms and therapeutic potential of histone demethylases in colorectal cancer.

## Key findings

- Histone demethylases regulate CRC progression through epigenetic changes.
- Targeting HDMs with inhibitors may reshape CRC tumorigenicity.
- Some HDMs and their mechanisms in CRC remain understudied.

## Abstract

Histone demethylases (HDMs) play a pivotal role in colorectal cancer (CRC) progression through dynamic epigenetic regulation. This review summarizes the role and therapeutic potential of HDM in CRC. HDMs primarily target lysine (K) for demethylation (lysine demethylase, KDM). The KDM family is divided into the lysine-specific demethylase family and the Jumonji C domain-containing family. HDMs play complex roles in CRC cell proliferation, invasion, migration, stemness, epithelial–mesenchymal transition, immune response, and chemoresistance through epigenetic regulation of different histone demethylation sites. Increasing evidence suggests that KDM may interact with certain factors and regulate CRC tumorigenesis by modulating multiple signaling pathways and affecting the transcription of target genes. These processes may be regulated by upstream genes and thus form a complex epigenetic regulatory network. However, the potential roles and regulatory mechanisms of some HDMs in CRC remain understudied. Preclinical studies have revealed that small-molecule inhibitors targeting HDM impact the activity of specific genes and pathways by inhibiting specific HDM expression, thereby reshaping the tumorigenic landscape of CRC. However, the clinical translational potential of these inhibitors remains unexplored. In conclusion, HDMs play a complex and critical role in CRC progression by dynamically regulating histone methylation patterns. These HDMs shape the malignant behavior of CRC by influencing the activity of key pathways and target genes through epigenetic reprogramming. Targeting HDM may be a promising direction for CRC treatment. Further exploration of the role of specific HDMs in CRC and the therapeutic potential of HDM-specific inhibitors is needed in the future.