title: Identification of miR-30d as a novel prognostic maker of prostate cancer.
abstract: Prostate cancer (PCa) is the most common malignant carcinoma that develops in men in Western countries. MicroRNA (miRNA) have the potential to be used as biomarkers and therapeutic targets for the treatment of various cancers. We found significantly higher expression of miR-30d in 3 PCa cell lines (PC3, DU145 and LNCaP) compared with 2 normal prostate cell lines (RWPE-1 and PrSc) using miRNA microarrays and qPCR. Clinicopathological study revealed that miR-30d expression levels were significantly higher in cancer tissue samples than in the paired normal controls (P = 0.03). Furthermore, the miR-30d-high group had shorter time to biochemical recurrence (P = 0.026). MiR-30d overexpressed PCa cells promoted proliferation and invasion in vitro. Inoculation of miR-30d depleted PCa cells dramatically reduced tumor volumes in vivo. Using reporter gene assay, we identified miR-30d as a downregulator of SOCS1 expression by directly binding to 3'-UTR of SOCS1. MiR-30d regulated the expression of phospho-STAT3, MMP-2 and MMP-9 through the downregulation of SOCS1. The levels of SOCS1 mRNA and protein were significantly down-regulated in prostate cancer tissues. Consistently, miR-30d expression was inversely correlated with SOCS1 expression (P = 0.03). The miR-30d-high/SOCS1-low group was associated with an increased risk of early biochemical recurrence (P = 0.0057). Taken together, miR-30d appears to be a novel independent prognostic marker of PCa progression that allows clinicians to identify patients who need more intensive treatments.
authors.affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: Naohito
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Hiroji
authors.initials: H
authors.lastname: Uemura
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nagahama
authors.forename: Koji
authors.initials: K
authors.lastname: Okudela
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Furuya
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ino
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ito
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirano
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Inayama
authors.forename: Ichiro
authors.initials: I
authors.lastname: Aoki
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kubota
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishiguro
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins