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Anti-silencing function 1B histone chaperone promotes cell proliferation and migration via activation of the AKT pathway in clear cell renal cell carcinoma.

Biochem. Biophys. Res. Commun.2019 Mar 26;511(1):165-172. Epub 2019 Feb 15
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摘要


Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies. Anti-silencing function 1B histone chaperone (ASF1B) has been reported to be involved in various diseases. However, its role in ccRCC is largely unknown. In the present study, using genetic data and clinical information obtained from the TCGA data portal and GEO database, we found that ASF1B was highly expressed in ccRCC cancer tissue compared with normal tissue, and ASF1B expression was positively correlated with tumor stage, tumor grade and patient survival. The function of ASF1B in cell proliferation and migration was assessed by pathological and molecular analyses. The results showed that ASF1B overexpression significantly enhanced the proliferation and migration of 786-O cells and Caki-1 cells, while silencing ASF1B expression significantly inhibited the proliferation and migration. In addition, ASF1B overexpression enhanced cell proliferation by upregulating PCNA and downregulating P27 expression and promoted cell migration by upregulating MMP2 and MMP9. Furthermore, the phosphorylation levels of protein kinase B (AKT) and P-P70 S6K1 were significantly upregulated in the ASF1B overexpression group. More importantly, AKT inhibitor blocked the promotional effect of ASF1B on proliferation and migration. In summary, the present study demonstrated that ASF1B overexpression promoted tumor cell proliferation and migration, which was dependent on the AKT/P70 S6K1 pathway.

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