title: Novel molecular targets regulated by tumor suppressors microRNA-1 and             microRNA-133a in bladder cancer.
abstract: Our expression signatures of human cancer including bladder cancer (BC)             revealed that the expression of microRNA-1 (miR-1) and microRNA-133a (miR-133a)             is significantly reduced in cancer cells. In the human genome, miR-1 and miR-133a             are located on the same chromosomal region (miR-1-2 and miR-133a-1 on 18q11.2,             and miR-1-1 and miR-133a-2 on 20q13.33) called cluster. In this study, we identified             the novel molecular targets commonly regulated by miR-1 and miR-133a in BC. Genome-wide             molecular target search and luciferase reporter assays showed that prothymosin-α             (PTMA) and purine nucleoside phosphorylase (PNP) are directly regulated by miR-1             and miR-133a. Silencing of these two genes significantly inhibited cell proliferation             and invasion, and increased apoptosis in BC cells. Immunohistochemistry showed             that PTMA expression levels were significantly higher in BC compared to normal             bladder epitheliums. PTMA and PNP were identified as new target genes regulated             by the miR-1 and miR-133a cluster in BC. These genes may function as oncogenes             contributing to cell proliferation and invasion in BC. Tumor suppressive miR-1             and miR-133a-mediated novel molecular targets may provide new insights into the             potential mechanisms of BC oncogenesis.
authors.affiliation: Department of Urology, Graduate School of Medical and Dental                     Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshino
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.forename: Hideo
authors.initials: H
authors.lastname: Hidaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiyomaru
authors.forename: Nijiro
authors.initials: N
authors.lastname: Nohata
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Miki
authors.initials: M
authors.lastname: Fuse
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004789:Enzyme Activation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D013947:Thymosin / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C544547:MIRN1 microRNA, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin; D011683:Purine-Nucleoside Phosphorylase; D020169:Caspases