Regulation of DU145 prostate cancer cell growth by Scm-like with four mbt domains 2

Abstract

Mammalian SFMBTs have been considered to be polycomb group repressors. However, molecular mechanisms underlying mammalian SFMBTs-mediated gene regulation and their biological function have not been characterized. In the present study, we identified YY1 and methylated histones as interacting proteins of human SFMBT2. We also found that human SFMBT2 binds preferentially to methylated histone H3 and H4 that are associated with transcriptional repression. Using DU145 prostate cancer cells as a model, we showed that SFMBT2 has a transcriptional repression activity on HOXB13 gene expression. In addition, occupancy of SFMBT2 coincided with enrichment of diand tri-methylated H3K9 and H4K20 as well as tri-methylated H3K27 at the HOXB13 gene promoter. When SFMBT2 was depleted by siRNA in DU145 prostate cancer cells, significant up-regulation of HOXB13 gene expression and decreased cell growth were observed. Collectively, our findings indicate that human SFMBT2 may regulate cell growth via epigenetic regulation of HOXB13 gene expression in DU145 prostate cancer cells.

SFMBT2 (Scm-like with four mbt domains 2) negatively regulates cell migration and invasion in prostate cancer cells

“…Since SFMBT2 is found to interact with YY1, which is a mammalian ortholog of Drosophila PHO [24, 34, 35], we further confirmed interaction of SFMBT2 with YY1 in LNCaP cells (Figure 3A). Consistent with a previous report [27], we also found that SFMBT2 interacts with RING1B/RNF2 E3 ubiquitin ligase, which mediates mono-ubiquitination of H2AK119, in LNCaP cells.…”

“…The mammalian PcG protein SFMBT2 has been shown to play an important role in prostate cancer cell growth through HOXB13 gene regulation via interaction with YY1 [24]. In this study, we further characterized the function of SFMBT2 in prostate cancer metastasis.…”

“…We found previously that mammalian SFMBT2, a polycomb gene (PcG), regulates cell growth in prostate cancer cells [24]. To further evaluate a possible role of SFMBT2 in prostate cancer progression, we first analyzed expression level of SFMBT2 in various prostate cancer cells lines.…”

“…Given that SFMBT2 participates in transcriptional repression, and MMPs are critical for cell migration and invasion through proteolysis of the extracellular matrix [24, 30, 31], we tested whether SFMBT2 regulates MMP gene expression. We examined expression of MMP genes including MMP-2 , MMP-3 , MMP-7 , MMP-9 , MMP-13 , MMP-14 , MMP-15 , and MMP-26 that are known to be up-regulated during prostate cancer progression [11].…”

“…SFMBT2 interacts with YY1 and regulates cell growth through repression of the HOXB13 gene in DU145 prostate cancer cells [24]. SFMBT has an MBT (malignant brain tumor) domain, which is important for gene regulation by recognizing and binding to methylated lysine residue of histone H3 and H4 tails [25].…”