Deregulated expression of selected histone methylases and demethylases in prostate carcinoma

Abstract

Prostate cancer (PCa), a leading cause of cancer-related morbidity and mortality, arises through the acquisition of genetic and epigenetic alterations. Deregulation of histone methyltransferases (HMTs) or demethylases (HDMs) has been associated with PCa development and progression. However, the precise influence of altered HMTs or HDMs expression and respective histone marks in PCa onset and progression remains largely unknown. To clarify the role of HMTs and HDMs in prostate carcinogenesis, expression levels of 37 HMTs and 20 HDMs were assessed in normal prostate and PCa tissue samples by RT-qPCR. SMYD3, SUV39H2, PRMT6, KDM5A, and KDM6A were upregulated, whereas KMT2A-E (MLL1-5) and KDM4B were downregulated in PCa, compared with normal prostate tissues. Remarkably, PRMT6 was the histone modifier that best discriminated normal from tumorous tissue samples. Interestingly, EZH2 and SMYD3 expression levels significantly correlated with less differentiated and more aggressive tumors. Remarkably, SMYD3 expression levels were of independent prognostic value for the prediction of disease-specific survival of PCa patients with clinically localized disease submitted to radical prostatectomy. We concluded that expression profiling of HMTs and HDMs, especially SMYD3, might be of clinical usefulness for the assessment of PCa patients and assist in pre-therapeutic decision-making.

A gain-of-function mouse model identifies PRMT6 as a NF-κB coactivator

“…It is, thus, likely that in tumors with high PRMT6 levels, the p53 pathway is epigenetically silenced. In keeping with this hypothesis, PRMT6 has been reported to be overexpressed in bladder and lung cancer cells (18), and more recently also been found to be dramatically elevated in prostate carcinomas (19). …”

“…However, the reduction of RelA levels by a knockdown approach did impair PRMT6 accumulation at target promoters. Notably, PRMT6 has been found overexpressed in many types of human cancers (2,19,44); therefore, the facilitation of NF-κB nuclear shuttling could be an important mechanism contributing to NF-κB-dependent gene activation in cancer (45). Cells lacking PRMT6 displayed reduced transcription of the IL-6 gene, strongly supporting a role for PRMT6 as a NF-κB coactivator.…”

MicroRNA hsa-miR-4674 in Hemolysis-Free Blood Plasma Is Associated with Distant Metastases of Prostatic Cancer

“…It has been shown that the expression of KMT2A together with other KMT2 family methyltransferases is lower in PC specimens in comparison with normal prostatic tissue [14]. Further studies will promote better understanding of the role of KMT2A in PC progress and development of the metastatic form of this tumor.…”

The Jumonji family: past, present and future of histone demethylases in cancer

“…The Genesapiens.org database shows that KDM5A is up-regulated in B-ALL, intestine and non-seminoma testicular cancer, while it is down-regulated in pancreatic cancer. JARID1B (KDM5B) is highly expressed in ductal breast cancer and is associated with breast and prostate carcinomas (70,71). KDM5B can also act as a transcriptional coactivator for AR (28,70).…”