Abstract
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 prostate cancer tissue compared with matched normal tissue. Ectopic JMJD1A expression in prostate cancer 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. In summary, our studies reveal JMJD1A plays an important role in regulating proliferation and progression of prostate cancer cells though Snail, and thus highlight JMJD1A as potential therapeutic target for advanced prostate cancer. 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 prostate cancer.
Highlights
Prostate cancer is one of the most commonly diagnosed malignancies and the second leading cause of cancer-related death in American men [1]
JMJD1A expression is elevated in prostate cancer tissue We previously found that JMJD1A played a key role in androgen receptor (AR)-FL
We analyzed the data from Oncomine and found JMJD1A mRNA levels were significantly upregulated in prostate cancer tissues compared with normal tissues (Fig. 1A)
Summary
Prostate cancer is one of the most commonly diagnosed malignancies and the second leading cause of cancer-related death in American men [1]. Androgen deprivation therapy (ADT) remains the primary clinical treatment for patients in the early stage of prostate cancer [2]. Most prostate cancer tumors become resistant to ADT and progress to a lethal stage called castrationresistant prostate cancer (CRPC), which is characterized by aggressive growth and distal organ metastasis, and is incurable [3]. Current therapies for CRPC, including treatment with newgeneration androgen receptor (AR)-pathway inhibitors (abiraterone or enzalutamide) and chemotherapy extend patient life by only a few month and benefit a little for the patients with metastatic CRPC [4, 5]. Note: Supplementary data for this article are available at Molecular Cancer Research Online (http://mcr.aacrjournals.org/).
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