title: Syndecan-1 responsive microRNA-126 and 149 regulate cell proliferation in prostate cancer.
abstract: MicroRNAs (miRNAs) are short (19-24 nt), low molecular weight RNAs that play important roles in the regulation of target genes associated with cell proliferation, differentiation, and development, by binding to the 3'-untranslated region of the target mRNAs. In this study, we examined the expression of miRNA-126 (miR-126) and miR-149 in prostate cancer, and investigated the molecular mechanisms by which they affect syndecan-1 in prostate cancer. Functional analysis of miR-126 and miR-149 was conducted in the prostate cancer cell lines, PC3, Du145, and LNCaP. The expression levels of SOX2, NANOG, Oct4, miR-126 and miR-149 were evaluated by quantitative RT-PCR. After silencing syndecan-1, miR-126, and/or miR-149 in the PC3 cells, cell proliferation, senescence, and p21 induction were assessed using the MTS assay, senescence-associated β-galactosidase (SA-β-Gal) assay, and immunocytochemistry, respectively. Compared to the Du145 and LNCaP cells, PC3 cells exhibited higher expression of syndecan-1. When syndecan-1 was silenced, the PC3 cells showed reduced expression of miR-126 and miR-149 most effectively. Suppression of miR-126 and/or miR-149 significantly inhibited cell growth via p21 induction and subsequently, induced senescence. The mRNA expression levels of SOX2, NANOG, and Oct4 were significantly increased in response to the silencing of miR-126 and/or miR-149. Our results suggest that miR-126 and miR-149 are associated with the expression of syndecan-1 in prostate cancer cells. These miRNAs promote cell proliferation by suppressing SOX2, NANOG, and Oct4. The regulation of these factors by miR-126 and miR-149 is essential for syndecan-1-mediated development of androgen-refractory prostate cancer.
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: Kiyohide
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Pathology, Nara Medical University School of Medicine, Nara, Japan. Electronic address: nkonishi@naramed-u.ac.jp.
authors.forename: Noboru
authors.initials: N
authors.lastname: Konishi
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D053668:Syndecan-1 / Q000502:physiology*; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018398:Homeodomain Proteins; C527111:MIRN126 microRNA, human; C551557:MIRN149 microRNA, human; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012333:RNA, Messenger; C508241:SDC1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D053668:Syndecan-1; D001616:beta-Galactosidase
keywords: MiR-126; MiR-149; MicroRNA; Prostate cancer; Syndecan-1