title: The tumor-suppressive microRNA-143/145 cluster inhibits cell migration and invasion by targeting GOLM1 in prostate cancer.
abstract: Our recent study of microRNA (miRNA) expression signature of prostate cancer (PCa) has revealed that the microRNA-143/145 (miR-143/145) cluster is significantly downregulated in cancer tissues, suggesting that these cluster miRNAs are candidate tumor suppressors. The aim of this study was to investigate the functional significance of the miR-143/145 cluster in PCa cells and to identify novel targets regulated by these cluster miRNAs in PCa. Restoration of miR-143 or miR-145 in PCa cell lines (PC3 and DU145) revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that Golgi membrane protein 1 (GOLM1) resembling a type II golgi transmembrane protein was a potential target of miR-143/145 cluster target gene. Gene expression studies and luciferase reporter assays showed that GOLM1 was directly regulated by the miR-143/145 cluster. Silencing of GOLM1 resulted in significant inhibition of cell migration and invasion in PCa cells. Furthermore, the expression of GOLM1 was upregulated in cancer tissues by immunohistochemistry. Loss of the tumor-suppressive miR-143/145 cluster enhanced cancer cell migration and invasion in PCa through directly regulating GOLM1. Our data on target genes regulated by the tumor-suppressive miR-143/145 cluster provide new insights into the potential mechanisms of PCa oncogenesis and metastasis.
authors.affiliation: Department of Urology, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Kojima
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshino
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Itesako
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiyomaru
authors.affiliation: Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Fuse
authors.affiliation: Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Nishikawa
authors.affiliation: Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Urology, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Naya
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D005810:Multigene Family; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*
chemical_list: C410824:GOLM1 protein, human; C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm