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 language | English |
|---|---|
| Pages (from-to) | 9628-9632 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 65 |
| Issue number | 21 |
| DOIs | |
| Publication status | Published - Nov 1 2005 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - A polycistronic MicroRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation
AU - Hayashita, Yoji
AU - Osada, Hirotaka
AU - Tatematsu, Yoshio
AU - Yamada, Hideki
AU - Yanagisawa, Kiyoshi
AU - Tomida, Shuta
AU - Yatabe, Yasushi
AU - Kawahara, Katsunobu
AU - Sekido, Yoshitaka
AU - Takahashi, Takashi
PY - 2005/11/1
Y1 - 2005/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=27544495514&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27544495514&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-05-2352
DO - 10.1158/0008-5472.CAN-05-2352
M3 - Article
C2 - 16266980
AN - SCOPUS:27544495514
VL - 65
SP - 9628
EP - 9632
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 21
ER -