title: A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation.
abstract: MicroRNAs (miRNAs) are small noncoding RNAs, thought to be involved in physiologic and developmental processes by negatively regulating expression of target genes. We have previously reported frequent down-regulation of the let-7 miRNA family in lung cancers and, in the present study, assessed alteration in a panel of 19 lung cancer cell lines. As a result, we found for the first time that the miR-17-92 cluster, which comprises seven miRNAs and resides in intron 3 of the C13orf25 gene at 13q31.3, is markedly overexpressed in lung cancers, especially with small-cell lung cancer histology. Southern blot analysis revealed the presence of increased gene copy numbers of the miRNA cluster in a fraction of lung cancer cell lines with overexpression. In addition, we were able to show predominant localization of C13orf25 transcripts within the nucleus and introduction of the expression construct of the miR-17-92 cluster, but not the putative open reading frame of C13orf25, enhancing lung cancer cell growth. These findings clearly suggest that marked overexpression of the miR-17-92 cluster with occasional gene amplification may play a role in the development of lung cancers, especially in their most aggressive form, small-cell lung cancer, and that the C13orf25 gene may well be serving as a vehicle in this regard.
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hayashita
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Osada
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tatematsu
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamada
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yanagisawa
authors.forename: Shuta
authors.initials: S
authors.lastname: Tomida
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Kawahara
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekido
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000235:genetics; D005784:Gene Amplification; D018628:Gene Dosage; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D016366:Open Reading Frames
chemical_list: D035683:MicroRNAs