Histone demethylase JMJD1A promotes tumor progression via activating Snail in prostate cancer

The histone demethylase JMJD1A plays a key functional role in spermatogenesis, sex determination, stem cell renewal and cancer via removing mono- and di-methyl groups from H3K9 to epigenetically control gene expression. However, its role in prostate cancer progression remains unclear. Here, we found JMJD1A was significantly elevated in PC tissue compared with matched normal tissue. Ectopic JMJD1A expression in PC cells promoted proliferation, migration and invasion in vitro, and tumorigenesis in vivo; JMJD1A knockdown exhibited the opposite effects. Mechanically, we revealed that JMJD1A directly interacted with the Snail gene promoter and regulated its transcriptional activity, promoting prostate cancer progression both in vitro and in vivo. Furthermore, we found that JMJD1A transcriptionally activated Snail expression via H3K9me1 and H3K9me2 demethylation at its special promoter region. Collectively, our findings identify a critical role for JMJD1A in regulating proliferation and progression of prostate cancer cells by controlling Snail expression at transcriptional level, and thus highlight JMJD1A as potential therapeutic target for advanced PC. Implications: Our studies identify that JMJD1A promotes the proliferation and progression of prostate cancer cells through enabling Snail transcriptional activation, and thus highlight JMJD1A as potential therapeutic target for advanced PC.