1602P - Syndecan-1 up-regulates microRNA-331-3p and mediates epithelial-to-mesenchymal transition in prostate cancer

Abstract

Syndecan-1 is an important regulator, and may contribute to various mechanisms in the progression of prostate cancer, such as cell growth, and epithelial-to-mesenchymal transition (EMT), through regulation of microRNAs (miRNAs). We recently found that miR-331-3p is down-regulated by syndecan-1 silencing in PC3 cells, based on an miRNA expression array and quantitative RT-PCR assay. The aim of the present study was to investigate whether syndecan-1-regulated miR-331-3p expression positively affects EMT. The expression of miR-331-3p, E-cadherin, and vimentin was detected in twenty-three prostate cancer tissues with in situ hybridization and immunohistochemistry. For functional analysis of miR-331-3p and syndecan-1, miR-331-3p precursor or syndecan-1 siRNA was transfected into PC3 cell lines. Cell proliferation and migration were evaluated with MTS assay and wound healing assay, respectively. For bioinformatics prediction, quantitative RT-PCR and luciferase assay were used to identify the target of the miRNA. In situ hybridization and immunohistochemistry of radical prostatectomy samples revealed miR-331-3p expression in cancer cells with high Gleason patterns, and EMT was demonstrated by decreased E-cadherin and increased vimentin staining. Overexpression of miR-331-3p up-regulated mesenchymal markers such as vimentin, N-cadherin, and Snail, and down-regulated epithelial markers such as E-cadherin and desmoplakin in the prostate cancer cell line PC3. We identified Neuropilin 2 (NRP2) and nucleus accumbens-associated protein 1 (NACC1) as putative target molecules in silico, as they were closely associated with the expression of miR-331-3p and TGF-&bgr;/Smad 4 signals. Syndecan-1 gene silencing decreased the levels of Dicer, which is involved in miRNA maturation. miR-331-3p can suppress tumor growth and the migration of prostate cancer cells by targeting NRP2 and NACC1, which may provide a potential therapeutic target for prostate cancer treatment. Moreover, syndecan-1-mediated miRNA maturation by Dicer and miR-331-3p-mediated EMT via effects on TGF-&bgr;/Smad 4 signaling are essential for the development of prostate cancer.