title: Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on microRNA expression signature in prostate cancer.
abstract: microRNAs (miRNAs) have key roles in human tumorigenesis, tumor progression and metastasis. miRNAs are aberrantly expressed in many human cancers and can function as tumor suppressors or oncogenes that target many cancer-related genes. This study seeks to identify novel miRNA-regulated molecular pathways in prostate cancer (PCa). The miRNA expression signature in clinical specimens of PCa showed that 56 miRNAs were significantly downregulated in PCa compared with non-PCa tissues. We focused on the top four downregulated miRNAs (miR-187, miR-205, miR-222 and miR-31) to investigate their functional significance in PCa cells. Expression levels of these four miRNAs were validated in PCa specimens (15 PCa tissues and 17 non-PCa tissues) to confirm that they were significantly reduced in these PCa tissues. Gain-of-function analysis demonstrated that miR-222 and miR-31 inhibited cell proliferation, invasion and migration in PCa cell lines (PC3 and DU145), suggesting that miR-222 and miR-31 may act as tumor suppressors in PCa. Genome-wide gene expression analysis using miR-222 or miR-31 transfectants to identify the pathways they affect showed that many cancer-related genes are regulated by these miRNAs in PC3 cells. Identification and categorization of the molecular pathways regulated by tumor suppressive miRNAs could provide new information about the molecular mechanisms of PCa tumorigenesis.
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Fuse
authors.forename: Satoko
authors.initials: S
authors.lastname: Kojima
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiyomaru
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshino
authors.forename: Nijiro
authors.initials: N
authors.lastname: Nohata
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Yukio
authors.initials: Y
authors.lastname: Naya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D003198:Computer Simulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015203:Reproducibility of Results
chemical_list: D035683:MicroRNAs; C571843:MIRN187 microRNA, human; C534425:MIR205, human; C525710:MIR222, human; C534612:MIRN31 microRNA, human