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Cancer Sci. 2017 Oct;108(10):2088-2101. doi: 10.1111/cas.13331. Epub 2017 Aug 19.

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

Author information

1
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
2
Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
3
Department of Urology, Teikyo University Chiba Medical Center, Ichihara, Japan.
4
Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan.
5
Department of Pathology, Teikyo University Chiba Medical Center, Ichihara, Japan.

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.

KEYWORDS:

miR-10a-5p ; MicroRNA; renal cell carcinoma; spindle and kinetochore-associated protein 1; tyrosine kinase inhibitor resistance

PMID:
28746769
PMCID:
PMC5623743
DOI:
10.1111/cas.13331
[Indexed for MEDLINE]
Free PMC Article

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