Identification of miR-30d as a novel prognostic maker of prostate cancer

// Naohito Kobayashi 1 , Hiroji Uemura 2 , Kiyotaka Nagahama 1 , Koji Okudela 3 , Mitsuko Furuya 1 , Yoko Ino 4 , Yusuke Ito 2 , Hisashi Hirano 4,7 , Yoshiaki Inayama 5 , Ichiro Aoki 1,7 , Yoji Nagashima 1 , Yoshinobu Kubota 2,7 , Hitoshi Ishiguro 2,6 1 Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Kanagawa, Japan 2 Department of Urology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Kanagawa, Japan 3 Department of Pathology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Kanagawa, Japan 4 Department of Supramolecular Biology, Yokohama City University, Tsurumi-ku, Yokohama, Kanagawa, Japan 5 Division of Anatomical and Surgical Pathology, Yokohama City University Hospital, Fukuura, Kanazawa-ku, Yokohama, Yokohama, Kanagawa, Japan 6 Photocatalyst Group, Kanagawa Academy of Science and Technology, Takatsu-ku, Kawasaki, Kanagawa, Japan 7 Advanced Medical Research Center, Yokohama City University, Fukuura, Kanazawa-ku, Yokohama, Kanagawa, Japan Correspondence: Hitoshi Ishiguro , email: // Keywords : miRNA-30d, prostate cancer, biochemical recurrence, SOCS1 Received : October 13, 2012, Accepted : November 15, 2012, Published : November 17, 2012 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.