AURKA promotes renal cell carcinoma progression via regulation of CCNB1 transcription.

ABSTRACT

AURKA is a member of the serine/threonine kinase family and its kinase activity is crucial for the progression of mitosis. Recent studies have highlighted the therapeutic significance of AURKA inhibition in multiple cancer types. However, the specific mechanisms by which AURKA contributes to the progression of renal cell carcinoma (RCC) have not been fully elucidated. In this study, AURKA expression level was identified in human RCC tissues by immunohistochemical (IHC) staining. The function of AURKA on cell malignant phenotypes was evaluated in vitro after AURKA inhibition. The subcutaneous xenograft was conducted to confirm the in vivo effect of AURKA knockdown on growth of RCC cells. Finally, Co-IP, luciferase assay and ChIP experiments were performed to reveal the regulatory mechanism of AURKA on CCNB1. Our results showed a significant upregulation of AURKA in RCC tissues and cell lines, and a high AURKA expression was associated with poor prognosis. AURKA knockdown inhibited RCC cell proliferation and migration, induced cell apoptosis, and led to G1/G2 phase arrest. This effect was further confirmed by the use of an AURKA inhibitor. Mechanistically, AURKA interacted with E2F1, and subsequently recruited it to the promoter region of CCNB1. CCNB1 expression was essential for AURKA-induced RCC progression. Collectively, our results suggested that AURKA plays an important role in development of RCC via regulating CCNB1 transcription.