1. Regulation of spindle and kinetochore‐associated protein 1 by antitumor miR‐10a‐5p in renal cell carcinoma
- Author
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Keiichi Koshizuka, Mayuko Kato, Takayuki Arai, Tetsuya Idichi, Satoko Kojima, Akira Kurozumi, Naohiko Seki, Atsushi Okato, Tomohiko Ichikawa, Kazuto Yamazaki, Yukio Naya, and Yasuo Ishida
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Chromosomal Proteins, Non-Histone ,miR‐10a‐5p ,urologic and male genital diseases ,Pathogenesis ,0302 clinical medicine ,Renal cell carcinoma ,Cell Movement ,Genetics, Genomics, and Proteomics ,3' Untranslated Regions ,Aged, 80 and over ,Gene knockdown ,tyrosine kinase inhibitor resistance ,MicroRNA ,General Medicine ,Middle Aged ,female genital diseases and pregnancy complications ,Kidney Neoplasms ,Gene Expression Regulation, Neoplastic ,Oncology ,030220 oncology & carcinogenesis ,Original Article ,Female ,Tyrosine kinase ,renal cell carcinoma ,Down-Regulation ,Biology ,03 medical and health sciences ,Downregulation and upregulation ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Neoplasm Invasiveness ,neoplasms ,Carcinoma, Renal Cell ,Protein Kinase Inhibitors ,Aged ,spindle and kinetochore‐associated protein 1 ,Original Articles ,medicine.disease ,Survival Analysis ,MicroRNAs ,030104 developmental biology ,Cell culture ,Drug Resistance, Neoplasm ,Cancer research ,Ectopic expression - 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.
- Published
- 2017