Abstract
Histone methyltransferases and demethylases regulate transcription by altering the epigenetic marks on histones in tumorigenesis. Members of the histone lysine(K)-specific demethylase 4 (KDM4) family are dysregulated in several types of cancer. Here, we report a novel role for KDM4B in mitochondrial apoptosis. In this study, we demonstrate that KDM4B is overexpressed in colorectal cancer (CRC) tissues. Decreased expression of KDM4B significantly promoted apoptosis of CRC cell lines. Moreover, our data indicate that HAX1 is required for KDM4B-mediated mitochondrial apoptosis. The transcription of HAX1 was directly activated by KDM4B. We also show that HAX1 is overexpressed in CRC tissues and is positively correlated with KMD4B expression. Collectively, we demonstrate that KDM4B may play an important role in mitochondrial apoptosis and represent a potential therapeutic cancer target in CRC.
Highlights
The role of epigenetic abnormalities in the initiation and progression of cancers is well recognized [1]
KDM4B mRNA levels were significantly higher in tumor samples than normal tissues (P = 0.0011, Figure 1A and 1B), and KDM4B protein was overexpressed in colorectal cancer (CRC) specimens, as assessed by western blot (Figure 1C)
It was gratifying that the analysis result was consistent with our findings (Supplementary Figure S1A ). These results show that KDM4B levels are significantly higher in colorectal cancer tissues than in corresponding non-neoplastic tissues
Summary
The role of epigenetic abnormalities in the initiation and progression of cancers is well recognized [1] Histone methylation, one such epigenetic modification, plays an important role in the functional regulation of gene expression, by activating or repressing transcription [2]. One such epigenetic modification, plays an important role in the functional regulation of gene expression, by activating or repressing transcription [2] This modification takes place on lysine residues, and prior to the discovery of histone demethylases, was thought to be essentially irreversible [3]. Histone demethylases remove methyl groups from the lysine residues of histone tails, thereby regulating the transcriptional activity of target genes [4, 5].
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