Epigenetic roles of KDM3B and KDM3C in tumorigenesis and their therapeutic implications

Area of Science:

• Epigenetics
• Molecular Biology
• Oncology

Background:

• Histone lysine demethylases (KDMs) are crucial epigenetic regulators involved in normal development and tumorigenesis.
• Most KDMs are Jumonji C domain-containing (JMJD) proteins that remove methyl groups from histones to control gene transcription.
• The KDM3 subfamily, including KDM3A, KDM3B, and KDM3C, specifically targets lysine 9 methylation on histone H3.

Purpose of the Study:

• To provide a comprehensive understanding of KDM3B and KDM3C involvement in oncology.
• To highlight the context-dependent, often overlooked, roles of KDM3B and KDM3C in tumorigenesis.
• To inform preclinical studies for developing novel cancer therapeutics targeting KDM3 proteins.

Main Methods:

• Literature review of functional studies on KDM3 proteins in cancer.
• Analysis of published data on KDM3B and KDM3C dysregulation and their oncogenic or tumor-suppressive functions.
• Synthesis of information regarding the therapeutic potential of targeting KDM3 family members.

Main Results:

• KDM3 proteins play vital roles in various biological processes, with dysregulation linked to infertility, obesity, metabolic disorders, heart disease, and cancer.
• While KDM3A is well-studied in cancer, KDM3B and KDM3C functions are relatively overlooked.
• KDM3B and KDM3C exhibit context-dependent activities, acting as either pro-tumorigenic or anti-tumorigenic factors in different cancer types.

Conclusions:

• KDM3B and KDM3C are significant, yet underappreciated, players in cancer development and progression.
• Understanding the specific roles of KDM3B and KDM3C in different cancer contexts is essential for targeted therapeutic strategies.
• Further research into KDM3B and KDM3C is warranted for the development of novel pharmacological approaches to combat cancer.