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Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells

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タイトル: Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells
著者: Takakura, Shu / Mitsutake, Norisato / Nakashima, Masahiro / Namba, Hiroyuki / Saenko, Vladimir A. / Rogounovitch, Tatiana I. / Nakazawa, Yuka / Hayashi, Tomayoshi / Ohtsuru, Akira / Yamashita, Shunichi
発行日: 2008年 6月
出版者: Blackwell Publishing
引用: Cancer Science, 99(6), pp.1147-1154; 2008
抄録: Micro RNAs (miRNAs) are non-coding small RNAs and constitute a novel class of negative gene regulators that are found in both plants and animals. Several miRNAs play crucial roles in cancer cell growth. To identify miRNAs specifically deregulated in anaplastic thyroid cancer (ATC) cells, we performed a comprehensive analysis of miRNA expressions in ARO cells and primary thyrocytes using miRNA microarrays. MiRNAs in a miR-17-92 cluster were overexpressed in ARO cells. We confirmed the overexpression of those miRNAs by Northern blot analysis in ARO and FRO cells. In 3 of 6 clinical ATC samples, miR-17-3p and miR-17-5p were robustly overexpressed in cancer lesions compared to adjacent normal tissue. To investigate the functional role of these miRNAs in ATC cells, ARO and FRO cells were transfected with miRNA inhibitors, antisense oligonucleotides containing locked nucleic acids. Suppression of miR-17-3p caused complete growth arrest, presumably due to caspase activation resulting in apoptosis. MiR-17-5p or miR-19a inhibitor also induced strong growth reduction, but only miR-17-5p inhibitor led to cellular senescence. On the other hand, miR-18a inhibitor only moderately attenuated the cell growth. Thus, we have clarified functional differences among the members of the cluster in ATC cells. In conclusion, these findings suggest that the miR-17-92 cluster plays an important role in certain types of ATCs and could be a novel target for ATC treatment.
キーワード: Anaplastic thyroid cancer / miRNA / miR-17-92 cluster / miR-17-3p / miR-17-5p / miR-19a
URI: http://hdl.handle.net/10069/22014
ISSN: 13479032
DOI: 10.1111/j.1349-7006.2008.00800.x
PubMed ID: 18429962
権利: © 2008 Japanese Cancer Association / The definitive version is available at www.blackwell-synergy.com
資料タイプ: Journal Article
原稿種類: author
出現コレクション:115 学術雑誌論文

引用URI : http://hdl.handle.net/10069/22014



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