Regulation of spindle and kinetochore‐associated protein 1 by antitumor miR‐10a‐5p in renal cell carcinoma. Issue 10 (19th August 2017)

• Record Type: Journal Article
• Authors: Arai, Takayuki; Okato, Atsushi; Kojima, Satoko; Idichi, Tetsuya; Koshizuka, Keiichi; Kurozumi, Akira; Kato, Mayuko; Yamazaki, Kazuto; Ishida, Yasuo; Naya, Yukio; Ichikawa, Tomohiko; Seki, Naohiko
• Is Part Of: Cancer science. Volume 108:Issue 10(2017)
• Page Start: 2088
• Page End: 2101
• Publication Date: 2017-08-19
• Subjects: MicroRNA -- miR‐10a‐5p -- renal cell carcinoma -- spindle and kinetochore‐associated protein 1 -- tyrosine kinase inhibitor resistance; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13331
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : 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. Abstract : miR‐10a‐5p was significantly downregulated in RCC specimens, and acted as an antitumor microRNA in RCC cells. SKA1 was identified as a candidate target gene regulated by miR‐10a‐5p, and functioned oncogenic in RCC cells. These findings showed that downregulation of miR‐10a‐5p and overexpression of the SKA1 axis were deeply involved in RCC pathogenesis.