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タイトル: Long non-coding RNA HOTAIR promotes cell migration by upregulating insulin growth factor–binding protein 2 in renal cell carcinoma
著者: Katayama, Hiromichi
Tamai, Keiichi
Shibuya, Rie
Nakamura, Mao
Mochizuki, Mai
Yamaguchi, Kazunori
Kawamura, Sadafumi
Tochigi, Tatsuo
Sato, Ikuro
Okanishi, Takamasa
Sakurai, Kunie
Fujibuchi, Wataru  kyouindb  KAKEN_id
Arai, Yoichi
Satoh, Kennichi
著者名の別形: 岡西, 孝真
桜井, 都衣
藤渕, 航
キーワード: Cell invasion
Long non-coding RNAs
Renal cell carcinoma
発行日: 20-Sep-2017
出版者: Springer Nature
誌名: Scientific Reports
巻: 7
論文番号: 12016
抄録: Renal cell carcinoma (RCC) is one of the most lethal urologic cancers. About one-third of RCC patients already have distal metastasis at the time of diagnosis. There is growing evidence that Hox antisense intergenic RNA (HOTAIR) plays essential roles in metastasis in several types of cancers. However, the precise mechanism by which HOTAIR enhances malignancy remains unclear, especially in RCC. Here, we demonstrated that HOTAIR enhances RCC-cell migration by regulating the insulin growth factor-binding protein 2 (IGFBP2) expression. HOTAIR expression in tumors was significantly correlated with nuclear grade, lymph-node metastasis, and lung metastasis. High HOTAIR expression was associated with a poor prognosis in both our dataset and The Cancer Genome Atlas dataset. Migratory capacity was enhanced in RCC cell lines in a HOTAIR-dependent manner. HOTAIR overexpression accelerated tumorigenicity and lung metastasis in immunodeficient mice. Microarray analysis revealed that IGFBP2 expression was upregulated in HOTAIR-overexpressing cells compared with control cells. The enhanced migration activity of HOTAIR-overexpressing cells was attenuated by IGFBP2 knockdown. IGFBP2 and HOTAIR were co-expressed in clinical RCC samples. Our findings suggest that the HOTAIR-IGFBP2 axis plays critical roles in RCC metastasis and may serve as a novel therapeutic target for advanced RCC.
著作権等: © The Author(s) 2017
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
URI: http://hdl.handle.net/2433/227884
DOI(出版社版): 10.1038/s41598-017-12191-z
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