title: Identification of direct targets for the miR-17-92 cluster by proteomic analysis.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally repress the expression of target genes. Many miRNAs have been implicated in a number of diseases, including cancers. The miR-17-92 miRNA cluster is known as a body of oncogenic miRNAs, and has been shown to be overexpressed in several cancers, including lung cancer. Although the overexpression of miR-17-92 is clearly implicated in the development of lung cancer, only a few direct targets for the miR-17-92 cluster have been identified thus far. In this study, we examined miR-17-92 target profiles in SBC-3 small-cell lung cancer cells using a quantitative proteomic strategy to identify direct targets of the miR-17-92 cluster. By knocking down the expression of endogenous miR-19a, miR-20a and miR-92-1, which are contained in the cluster, 112 up-regulated proteins were detected and also identified as potential targets of these miRNAs. Among these candidate targets, we validated one direct target, RAB14. In conclusion, these findings suggest that proteomic approaches are valuable for identifying direct miRNA targets, and we were able to identify a novel direct target for the miR-92-1 using our proteomic strategy.
authors.affiliation: Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kanzaki
authors.forename: Sachio
authors.initials: S
authors.lastname: Ito
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hanafusa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Jitsumori
authors.forename: Seiji
authors.initials: S
authors.lastname: Tamaru
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ouchida
mesh_terms: D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism*
chemical_list: C524941:MIRN17 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D020543:Proteome