title: Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 in bladder cancer.
abstract: Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep-sequencing revealed that two miRNA, microRNA-139-5p/microRNA-139-3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNA and their modulation of cancer networks in BC cells. Functional assays of BC cells were performed using transfection of mature miRNA or small interfering RNA (siRNA). Genome-wide gene expression analysis, in silico analysis and dual-luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan-Meier method. Gain-of-function studies showed that miR-139-5p and miR-139-3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR-139-5p and miR-139-3p. Kaplan-Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR-139-5p or miR-139-3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNA and might be a good prognostic marker for survival of BC patients.
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Yonemori
authors.affiliation: Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
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: Ryosuke
authors.initials: R
authors.lastname: Matsushita
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Miyamoto
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 Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan. enokida@m.kufm.kagoshima-u.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053507:Matrix Metalloproteinase 11 / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: C555098:MIRN139 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D053507:Matrix Metalloproteinase 11
keywords: Bladder cancer; MMP11; miR-139; miRNA; tumour suppressors