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

2017; Wiley; Volume: 108; Issue: 10 Linguagem: Inglês

10.1111/cas.13331

1349-7006

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

Epigenetics and DNA Methylation

Analysis of our original micro RNA (mi RNA ) expression signature of patients with advanced renal cell carcinoma ( RCC ) showed that micro RNA ‐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 mi RNA 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 ( SKA 1 ) was identified as an antitumor miR‐10a‐5p target by genome‐based approaches, and direct regulation was validated by luciferase reporter assays. Knockdown of SKA 1 inhibited cancer cell migration and invasion in RCC cells. Overexpression of SKA 1 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 SKA 1 were significantly associated with overall survival in patients with RCC . These findings showed that downregulation of miR‐10a‐5p and overexpression of the SKA 1 axis were highly involved in RCC pathogenesis and resistance to TKI treatment in RCC .