Histone demethylase JMJD2C: epigenetic regulators in tumors

Abstract

Histone methylation is one of the major epigenetic modifications, and various histone methylases and demethylases participate in the epigenetic regulating. JMJD2C has been recently identified as one of the histone lysine demethylases. As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes. JMJD2C was firstly found to involve in embryonic development and stem cell regulation. Afterwards, aberrant status of JMJD2C histone methylation was observed during the formation and development of various tumors, and it has been reported to play crucial roles in the progression of breast cancer, prostate carcinomas, osteosarcoma, blood neoplasms and so on, indicating that JMJD2C represents a promising anti-cancer target. In this review, we will focus on the research progress and prospect of JMJD2C in tumors, and provide abundant evidence for the functional application and therapeutic potential of targeting JMJD2C in tumors.

Proteomic and Transcriptomic Profiling Reveals Mitochondrial Oxidative Phosphorylation as Therapeutic Vulnerability in Androgen Receptor Pathway Active Prostate Tumors

“…Antimycin, a mitochondrial electron transport chain inhibitor, has been shown to prevent the growth of lung cancer cells [ 33 ]. GSK-J4 is an inhibitor of several histone demethylases and has been proposed as a potential cancer therapeutic agent [ 34 ]. We found that all AR-positive cell lines tested were more sensitive to inhibition of mTOR (EC 50 < 100 nM) relative to the NCI-H660 cell line (EC 50 > 100 µM) ( Figure 4 ).…”

FDHE-IW: A Fast Approach for Detecting High-Order Epistasis in Genome-Wide Case-Control Studies

“…CFH was also found to have a novel connection with the JMJD2C gene, a histone lysine demethylase. JMJD2C has been reported to play a crucial role in the progression of breast cancer, prostate carcinomas, osteosarcoma, and blood neoplasms, thus indicating that JMJD2C represents a promising anti-cancer target [ 39 , 40 , 41 ]. These findings also suggest that JMJD2C may have an important role in AMD.…”

KDM4C Contributes to Trophoblast-like Stem Cell Conversion from Porcine-Induced Pluripotent Stem Cells (piPSCs) via Regulating CDX2

“…At first, we detected the expression of histone-modifying enzymes in E-piPSCs and found that KDM4C could be a candidate. Unlike many other histone-modifying enzymes, KDM4C demethylates H3K36me3/2 and H3K9me3 at the same time [ 22 ]. However, the function of KDM4C is always hard to determine.…”