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Da Peng Yu, Yan Zhou
(Department of Surgical Urology, The First People’s Hospital of Jining City, Jining, Shandong, China (mainland))
Med Sci Monit 2018; 24:8213-8223
Clear cell renal cell carcinoma (ccRCC) is usually incurable once it progresses to metastatic stage. Hence, in-depth investigations to reveal the precise molecular mechanisms behind the metastasis of ccRCC are required to improve the therapeutic outcome of ccRCC.
MATERIAL AND METHODS: The level of astrocyte elevated gene 1 (AEG-1) in ccRCC tissues and cell lines was determined by quantitative real-time PCR (qRT-PCR) assay. The MTS, colony formation, wound-healing, and Transwell invasion assays were used to assess the role of AEG-1 in ccRCC cells growth, migration, and invasion in vitro, respectively. Xenograft model and lung metastasis models were constructed to analyze the functions of AEG-1 in ccRCC cells growth and metastasis in vivo.
RESULTS: We found that AEG-1 was overexpressed in ccRCC and was associated with the progression of ccRCC. Knocked-down AEG-1 impaired the migration and invasion of ccRCC cells in vitro. Furthermore, under-expression of AEG-1 caused complete inhibition of ccRCC cells growth and metastasis in vivo. In contrast, overexpression of AEG-1 significantly increased the migration and invasion ability of ccRCC cells in vitro. Finally, we revealed that AEG-1 boosted the metastatic ability of ccRCC cells via regulating Notch homolog 1 (Notch1).
CONCLUSIONS: The AEG-1/Notch1 signaling axis plays a vital role in ccRCC cell growth and metastasis.