Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Apr 9;47(4):267.
doi: 10.3390/cimb47040267.

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

Yuanbin Liu  1 , Min Huang  1 , Xia Tian  1 , Xiaodong Huang  1
Affiliations
Review

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

Yuanbin Liu et al. Curr Issues Mol Biol. .

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.

Keywords: colorectal cancer; epigenetics; histone demethylases; histone demethylation; lysine demethylases.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest in this study.

Figures

Figure 1
Figure 1
Mechanistic overview of HDMs in CRC.
Figure 2
Figure 2
HDM classification, composition, and substrate overview.
Figure 3
Figure 3
HDM inhibitors and their corresponding HDM targets in CRC.
See this image and copyright information in PMC

References

    1. Bray F., Laversanne M., Sung H., Ferlay J., Siegel R.L., Soerjomataram I., Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2024;74:229–263. doi: 10.3322/caac.21834. - DOI - PubMed
    1. Yang Y., Gao Z., Huang A., Shi J., Sun Z., Hong H., Gu J. Epidemiology and early screening strategies for colorectal cancer in China. Chin. J. Cancer Res. 2023;35:606–617. doi: 10.21147/j.issn.1000-9604.2023.06.05. - DOI - PMC - PubMed
    1. Xu L., Zhao J., Li Z., Sun J., Lu Y., Zhang R., Zhu Y., Ding K., Rudan I., Theodoratou E., et al. National and subnational incidence, mortality and associated factors of colorectal cancer in China: A systematic analysis and modelling study. J. Glob. Health. 2023;13:04096. doi: 10.7189/jogh.13.04096. - DOI - PMC - PubMed
    1. Kuipers E.J., Grady W.M., Lieberman D., Seufferlein T., Sung J.J., Boelens P.G., Van De Velde C.J.H., Watanabe T. Colorectal cancer. Nat. Rev. Dis. Primers. 2015;1:15065. doi: 10.1038/nrdp.2015.65. - DOI - PMC - PubMed
    1. Eng C., Yoshino T., Ruíz-García E., Mostafa N., Cann C.G., O’Brian B., Benny A., O Perez R., Cremolini C. Colorectal cancer. Lancet. 2024;404:294–310. doi: 10.1016/S0140-6736(24)00360-X. - DOI - PubMed

LinkOut - more resources