Advances in Histone Demethylase KDM3A As a Cancer Therapeutic Target

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2020 May 2

PMID 32354028

Citations 29

Authors

Jung Yoo

Yu Hyun Jeon

Ha Young Cho

Sang Wu Lee

Go Woon Kim

Dong Hoon Lee

So Hee Kwon

Affiliations

Soon will be listed here.

Abstract

Lysine-specific histone demethylase 3 (KDM3) subfamily proteins are H3K9me2/me1 histone demethylases that promote gene expression. The KDM3 subfamily primarily consists of four proteins (KDM3A-D). All four proteins contain the catalytic Jumonji C domain (JmjC) at their C-termini, but whether KDM3C has demethylase activity is under debate. In addition, KDM3 proteins contain a zinc-finger domain for DNA binding and an LXXLL motif for interacting with nuclear receptors. Of the KDM3 proteins, KDM3A is especially deregulated or overexpressed in multiple cancers, making it a potential cancer therapeutic target. However, no KDM3A-selective inhibitors have been identified to date because of the lack of structural information. Uncovering the distinct physiological and pathological functions of KDM3A and their structure will give insight into the development of novel selective inhibitors. In this review, we focus on recent studies highlighting the oncogenic functions of KDM3A in cancer. We also discuss existing KDM3A-related inhibitors and review their potential as therapeutic agents for overcoming cancer.

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