A polycistronic MicroRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation

Yoji Hayashita, Hirotaka Osada, Yoshio Tatematsu, Hideki Yamada, Kiyoshi Yanagisawa, Shuta Tomida, Yasushi Yatabe, Katsunobu Kawahara, Yoshitaka Sekido, Takashi Takahashi

Research output: Contribution to journalArticle

1219 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9628-9632
Number of pages5
JournalCancer Research
Volume65
Issue number21
DOIs
Publication statusPublished - Nov 1 2005
Externally publishedYes

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MicroRNAs
Lung Neoplasms
Cell Proliferation
Small Cell Lung Carcinoma
Cell Line
Small Untranslated RNA
Gene Dosage
Gene Amplification
Neoplasm Genes
Southern Blotting
Introns
Open Reading Frames
Histology
Down-Regulation
Gene Expression
Growth
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A polycistronic MicroRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. / Hayashita, Yoji; Osada, Hirotaka; Tatematsu, Yoshio; Yamada, Hideki; Yanagisawa, Kiyoshi; Tomida, Shuta; Yatabe, Yasushi; Kawahara, Katsunobu; Sekido, Yoshitaka; Takahashi, Takashi.

In: Cancer Research, Vol. 65, No. 21, 01.11.2005, p. 9628-9632.

Research output: Contribution to journalArticle

Hayashita, Y, Osada, H, Tatematsu, Y, Yamada, H, Yanagisawa, K, Tomida, S, Yatabe, Y, Kawahara, K, Sekido, Y & Takahashi, T 2005, 'A polycistronic MicroRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation', Cancer Research, vol. 65, no. 21, pp. 9628-9632. https://doi.org/10.1158/0008-5472.CAN-05-2352
Hayashita, Yoji ; Osada, Hirotaka ; Tatematsu, Yoshio ; Yamada, Hideki ; Yanagisawa, Kiyoshi ; Tomida, Shuta ; Yatabe, Yasushi ; Kawahara, Katsunobu ; Sekido, Yoshitaka ; Takahashi, Takashi. / A polycistronic MicroRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. In: Cancer Research. 2005 ; Vol. 65, No. 21. pp. 9628-9632.
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