DOI: 10.1158/0008-5472.can-05-2352. A Polycistronic MicroRNA Cluster, <i>miR-17-92</i>, Is Overexpressed in Human Lung Cancers and Enhances Cell Proliferation

A Polycistronic MicroRNA Cluster, miR-17-92, Is Overexpressed in Human Lung Cancers and Enhances Cell Proliferation

10.1158/0008-5472.can-05-2352

Crossref journal-article

American Association for Cancer Research (AACR)

Cancer Research (1086)

Abstract

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.

Bibliography

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, 65(21), 9628â9632.

Authors 10

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

References 20 Referenced 1,258

Osada H, Takahashi T. Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer. Oncogene 2002; 21: 7421–34. (10.1038/sj.onc.1205802)
Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 2002; 99: 15524–9. (10.1073/pnas.242606799)
Michael MZ, O'Connor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 2003; 1: 882–91.
Calin GA, Sevignani C, Dumitru CD, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 2004; 101: 2999–3004. (10.1073/pnas.0307323101)
Eis PS, Tam W, Sun L, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A 2005; 102: 3627–32. (10.1073/pnas.0500613102)
Ambros V. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell 2003; 113: 673–6. (10.1016/S0092-8674(03)00428-8)
Takamizawa J, Konishi H, Yanagisawa K, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 2004; 64: 3753–6. (10.1158/0008-5472.CAN-04-0637)
Karube Y, Tanaka H, Osada H, et al. Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci 2005; 96: 111–5. (10.1111/j.1349-7006.2005.00015.x)
Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell 2003; 115: 787–98. (10.1016/S0092-8674(03)01018-3)
Masuda A, Kondo M, Saito T, et al. Establishment of human peripheral lung epithelial cell lines (HPL1) retaining differentiated characteristics and responsiveness to epidermal growth factor, hepatocyte growth factor, and transforming growth factor b1. Cancer Res 1997; 57: 4898–904.
Ke Y, Reddel RR, Gerwin BI, et al. Human bronchial epithelial cells with integrated SV40 virus T antigen genes retain the ability to undergo squamous differentiation. Differentiation 1988; 38: 60–6. (10.1111/j.1432-0436.1988.tb00592.x)
Ota A, Tagawa H, Karnan S, et al. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res 2004; 64: 3087–95. (10.1158/0008-5472.CAN-03-3773)
Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120: 15–20. (10.1016/j.cell.2004.12.035)
Krek A, Grun D, Poy MN, et al. Combinatorial microRNA target predictions. Nat Genet 2005; 37: 495–500. (10.1038/ng1536)
Lim LP, Lau NC, Garrett-Engele P, et al. Microarray analysis shows that some microRNAs down-regulate large numbers of target mRNAs. Nature 2005; 433: 769–73. (10.1038/nature03315)
He L, Thomson JM, Hemann MT, et al. A microRNA polycistron as a potential human oncogene. Nature 2005; 435: 828–33. (10.1038/nature03552)
O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005; 435: 839–43. (10.1038/nature03677)
Takahashi T, Obata Y, Sekido Y, et al. Expression and amplification of myc gene family in small cell lung cancer and its relation to biological characteristics. Cancer Res 1989; 49: 2683–8.
Sekido Y, Takahashi T, Makela TP, et al. Complex intrachromosomal rearrangement in the process of amplification of the L-myc gene in small-cell lung cancer. Mol Cell Biol 1992; 12: 1747–54. (10.1128/mcb.12.4.1747-1754.1992)
Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 microRNA family. Cell 2005; 120: 635–47. (10.1016/j.cell.2005.01.014)

Dates

Type	When
Created	19 years, 10 months ago (Nov. 1, 2005, 8:38 p.m.)
Deposited	3 years, 2 months ago (June 17, 2022, 3:07 p.m.)
Indexed	2 days, 17 hours ago (Sept. 3, 2025, 6:59 a.m.)
Issued	19 years, 10 months ago (Nov. 1, 2005)
Published	19 years, 10 months ago (Nov. 1, 2005)
Published Online	19 years, 10 months ago (Nov. 1, 2005)
Published Print	19 years, 10 months ago (Nov. 1, 2005)

Funders 0

None

BibTeX

@article{Hayashita_2005, title={A Polycistronic MicroRNA Cluster, miR-17-92, Is Overexpressed in Human Lung Cancers and Enhances Cell Proliferation}, volume={65}, ISSN={1538-7445}, url={http://dx.doi.org/10.1158/0008-5472.can-05-2352}, DOI={10.1158/0008-5472.can-05-2352}, number={21}, journal={Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Hayashita, Yoji and Osada, Hirotaka and Tatematsu, Yoshio and Yamada, Hideki and Yanagisawa, Kiyoshi and Tomida, Shuta and Yatabe, Yasushi and Kawahara, Katsunobu and Sekido, Yoshitaka and Takahashi, Takashi}, year={2005}, month=nov, pages={9628–9632} }

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