論文

査読有り 国際誌
2017年10月

Regulation of spindle and kinetochore-associated protein 1 by antitumor miR-10a-5p in renal cell carcinoma.

Cancer science
  • Takayuki Arai
  • ,
  • Atsushi Okato
  • ,
  • Satoko Kojima
  • ,
  • Tetsuya Idichi
  • ,
  • Keiichi Koshizuka
  • ,
  • Akira Kurozumi
  • ,
  • Mayuko Kato
  • ,
  • Kazuto Yamazaki
  • ,
  • Yasuo Ishida
  • ,
  • Yukio Naya
  • ,
  • Tomohiko Ichikawa
  • ,
  • Naohiko Seki

108
10
開始ページ
2088
終了ページ
2101
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/cas.13331

Analysis of our original microRNA (miRNA) expression signature of patients with advanced renal cell carcinoma (RCC) showed that microRNA-10a-5p (miR-10a-5p) was significantly downregulated in RCC specimens. The aims of the present study were to investigate the antitumor roles of miR-10a-5p and the novel cancer networks regulated by this miRNA in RCC cells. Downregulation of miR-10a-5p was confirmed in RCC tissues and RCC tissues from patients treated with tyrosine kinase inhibitors (TKI). Ectopic expression of miR-10a-5p in RCC cell lines (786-O and A498 cells) inhibited cancer cell migration and invasion. Spindle and kinetochore-associated protein 1 (SKA1) was identified as an antitumor miR-10a-5p target by genome-based approaches, and direct regulation was validated by luciferase reporter assays. Knockdown of SKA1 inhibited cancer cell migration and invasion in RCC cells. Overexpression of SKA1 was observed in RCC tissues and TKI-treated RCC tissues. Moreover, analysis of The Cancer Genome Atlas database demonstrated that low expression of miR-10a-5p and high expression of SKA1 were significantly associated with overall survival in patients with RCC. These findings showed that downregulation of miR-10a-5p and overexpression of the SKA1 axis were highly involved in RCC pathogenesis and resistance to TKI treatment in RCC.

リンク情報
DOI
https://doi.org/10.1111/cas.13331
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28746769
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623743

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