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Published on: September 10, 2014
KDM5 demethylases and their role in cancer cell chemoresistance
Johana Plch1, Jan Hrabeta1, Tomas Eckschlager1
1Department of Pediatric Hematology and Oncology, 2nd Medical Faculty and University Hospital Motol, Prague, Czech Republic.
Abstract:
Histone methylation is important in the regulation of genes expression, and thus its dysregulation has been observed in various cancers. KDM5 enzymes are capable of removing tri- and di- methyl marks from lysine 4 on histone H3 (H3K4) which makes them potential players in the downregulation of tumor suppressors, but could also suggest that their activity repress oncogenes. Depending on the methylation site, their effect on transcription can be either activating or repressing. There is emerging evidence for deregulation of KDM5A/B/C/D and important phenotypic consequences in various types of cancer. It has been suggested that the KDM5 family of demethylases plays a role in the appearance of drug tolerance. Drug resistance remains a challenge to successful cancer treatment. This review summarizes recent advances in understanding the functions of KDM5 histone demethylases in cancer chemoresistance and potential therapeutic targeting of these enzymes, which seems to prevent the emergence of a drug-resistant population.
Insights
Histone demethylases KDM5 are implicated in cancer drug resistance by regulating gene expression. Targeting these enzymes may prevent the development of drug-tolerant cancer cells.
Area of Science:
- Epigenetics
- Cancer Biology
- Molecular Oncology
Background:
- Histone methylation regulates gene expression; its dysregulation is linked to cancer.
- KDM5 enzymes remove H3K4 methylation marks, influencing gene transcription.
- KDM5A/B/C/D deregulation is observed in various cancers with significant phenotypic consequences.
Purpose of the Study:
- To review recent advances in understanding KDM5 histone demethylases in cancer chemoresistance.
- To explore the potential therapeutic targeting of KDM5 enzymes to combat drug resistance.
Main Methods:
- Literature review of studies on KDM5 function in cancer.
- Analysis of evidence linking KDM5 activity to drug tolerance and resistance.
- Examination of therapeutic strategies targeting KDM5 enzymes.
Main Results:
- KDM5 enzymes play a role in the emergence of drug tolerance in cancer.
- Their dual role in regulating tumor suppressors and oncogenes contributes to cancer progression.
- Targeting KDM5 may prevent the development of drug-resistant cancer populations.
Conclusions:
- KDM5 histone demethylases are critical regulators in cancer chemoresistance.
- Therapeutic targeting of KDM5 offers a promising strategy to overcome drug resistance and improve cancer treatment outcomes.
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