title: Syndecan-1 up-regulates microRNA-331-3p and mediates epithelial-to-mesenchymal transition in prostate cancer.
abstract: MicroRNAs (miRNAs) are small noncoding RNAs with a length of approximately 19-24 nucleotides that regulate gene expression through translational inhibition and contribute to the progression of various tumors including prostate cancer. Aberrant expression of miRNAs has been implicated in the progression and metastasis of prostate cancer. The present study aimed to investigate whether miR-331-3p controlled by syndecan-1 positively affects the epithelial-to-mesenchymal transition (EMT). Overexpression of miR-331-3p upregulated mesenchymal markers such as vimentin, N-cadherin, and snail and downregulated epithelial markers such as E-cadherin and desmoplakin in the prostate cancer cell line PC3. We identified Neuropilin 2 and nucleus accumbens-associated protein 1 as putative target molecules in silico, as they were closely associated with the expression of miR-331-3p and TGF-β/Smad 4 signals. In situ hybridization and immunohistochemistry of radical prostatectomy samples revealed miR-331-3p in cancer cells with high Gleason patterns, in which EMT was demonstrated by decreased E-cadherin, and increased vimentin staining. Syndecan-1 gene silencing decreased levels of Dicer, which is involved in miRNA maturation. MiR-331-3p-mediated miRNA maturation and enhanced EMT via effects on TGF-β/Smad 4 and Dicer are essential for the development of prostate cancer mediated by syndecan-1. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Pathology, Nara Medical University School of Medicine, Nara, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Pathology, Nara Medical University School of Medicine, Nara, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Pathology, Nara Medical University School of Medicine, Nara, Japan.|Department of Urology, Nara Medical University School of Medicine, Nara, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tatsumi
authors.affiliation: Department of Urology, Nara Medical University School of Medicine, Nara, Japan.
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Department of Urology, Nara Medical University School of Medicine, Nara, Japan.
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Pathology, Nara Medical University School of Medicine, Nara, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Konishi
mesh_terms: D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D039943:Neuropilin-2 / Q000235:genetics; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012097:Repressor Proteins / Q000235:genetics; D043244:Ribonuclease III / Q000235:genetics; D053668:Syndecan-1 / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: C544460:MIRN331 microRNA, human; D035683:MicroRNAs; C516477:NACC1 protein, human; D009363:Neoplasm Proteins; D039943:Neuropilin-2; D012097:Repressor Proteins; D053668:Syndecan-1; D016212:Transforming Growth Factor beta; D043244:Ribonuclease III
keywords: EMT; TGF-β; miR-331-3p; prostate cancer; syndecan-1