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组蛋白伴侣 Anti-silencing function 1B 通过激活 AKT 通路促进透明细胞肾细胞癌的细胞增殖和迁移。

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

机构信息

Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, 430060, China.

Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, 430060, China.

出版信息

Biochem Biophys Res Commun. 2019 Mar 26;511(1):165-172. doi: 10.1016/j.bbrc.2019.02.060. Epub 2019 Feb 15.

DOI:10.1016/j.bbrc.2019.02.060
PMID:30777326
Abstract

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.

摘要

透明细胞肾细胞癌(ccRCC)是最常见的恶性肿瘤之一。抗沉默功能 1B 组蛋白伴侣(ASF1B)已被报道参与各种疾病。然而,其在 ccRCC 中的作用在很大程度上尚不清楚。在本研究中,我们使用来自 TCGA 数据门户和 GEO 数据库的遗传数据和临床信息,发现与正常组织相比,ASF1B 在 ccRCC 癌组织中高表达,并且 ASF1B 表达与肿瘤分期、肿瘤分级和患者生存呈正相关。通过病理和分子分析评估了 ASF1B 在细胞增殖和迁移中的功能。结果表明,ASF1B 过表达显著增强了 786-O 细胞和 Caki-1 细胞的增殖和迁移能力,而沉默 ASF1B 表达则显著抑制了增殖和迁移。此外,ASF1B 过表达通过上调 PCNA 和下调 P27 表达增强细胞增殖,并通过上调 MMP2 和 MMP9 促进细胞迁移。此外,ASF1B 过表达组中蛋白激酶 B(AKT)和 P-P70 S6K1 的磷酸化水平显著上调。更重要的是,AKT 抑制剂阻断了 ASF1B 对增殖和迁移的促进作用。总之,本研究表明 ASF1B 过表达促进了肿瘤细胞的增殖和迁移,这依赖于 AKT/P70 S6K1 通路。

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