title: The microRNA profile of prostate carcinoma obtained by deep sequencing.
abstract: Prostate cancer is a leading cause of tumor mortality. To characterize the underlying molecular mechanisms, we have compared the microRNA (miRNA) profile of primary prostate cancers and noncancer prostate tissues using deep sequencing. MiRNAs are small noncoding RNAs of 21 to 25 nucleotides that regulate gene expression through the inhibition of protein synthesis. We find that 33 miRNAs were upregulated or downregulated >1.5-fold. The deregulation of selected miRNAs was confirmed by both Northern blotting and quantitative reverse transcription-PCR in established prostate cancer cell lines and clinical tissue samples. A computational search indicated the 3'-untranslated region (UTR) of the mRNA for myosin VI (MYO6) as a potential target for both miR-143 and miR-145, the expression of which was reduced in the tumor tissues. Upregulation of myosin VI in prostate cancer was previously shown by immunohistochemistry. The level of MYO6 mRNA was significantly induced in all primary tumor tissues compared with the nontumor tissue from the same patient. This finding was matched to the upregulation of myosin VI in established prostate cancer cell lines. In luciferase reporter analysis, we find a significant negative regulatory effect on the MYO6 3'UTR by both miR-143 and miR-145. Mutation of the potential binding sites for miR-143 and miR-145 in the MYO6 3'UTR resulted in a loss of responsiveness to the corresponding miRNA. Our data indicate that miR-143 and miR-145 are involved in the regulation of MYO6 expression and possibly in the development of prostate cancer.
authors.affiliation: Department of Virology, University of Saarland Medical School, Homburg/Saar, Germany.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Szczyrba
authors.forename: Elke
authors.initials: E
authors.lastname: Löprich
authors.forename: Sven
authors.initials: S
authors.lastname: Wach
authors.forename: Volker
authors.initials: V
authors.lastname: Jung
authors.forename: Gerhard
authors.initials: G
authors.lastname: Unteregger
authors.forename: Stephanie
authors.initials: S
authors.lastname: Barth
authors.forename: Rainer
authors.initials: R
authors.lastname: Grobholz
authors.forename: Wolf
authors.initials: W
authors.lastname: Wieland
authors.forename: Robert
authors.initials: R
authors.lastname: Stöhr
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grässer
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015533:Transcriptional Activation / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C089785:myosin VI; D018995:Myosin Heavy Chains