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

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Translational Research
Presenter Tomomi Fujii
Citation Annals of Oncology (2016) 27 (6): 545-551. 10.1093/annonc/mdw393
Authors T. Fujii1, K. Shimada1, Y. Tatsumi1, N. Tanaka2, K. Fujimoto3, N. Konishi1
  • 1Pathology, Nara Medical University, 634-8521 - Nara/JP
  • 2Urology, Nara Medical University Hospital, 634-8522 - Kashihara/JP
  • 3Urology, Nara Medical University Hospital, Kashihara/JP

Abstract

Background

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.

Methods

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.

Results

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-ß/Smad 4 signals. Syndecan-1 gene silencing decreased the levels of Dicer, which is involved in miRNA maturation.

Conclusions

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-ß/Smad 4 signaling are essential for the development of prostate cancer.

Clinical trial identification

Legal entity responsible for the study

Nara Medical University School of Medicine, Nara, Japan

Funding

Grant-in-Aid from the Ministry of Educaion, Culture, Sports, Science and Technology, Japan (26462424)

Disclosure

All authors have declared no conflicts of interest.