基础医学与临床 ›› 2018, Vol. 38 ›› Issue (6): 764-770.

• 研究论文 • 上一篇    下一篇

YAF2靶向cyclin D1表达促进肿瘤细胞增殖

侯丛丛,马晓骊,陈虹,黄秉仁,陈等   

  1. 中国医学科学院基础医学研究所
  • 收稿日期:2018-03-02 修回日期:2018-03-27 出版日期:2018-06-05 发布日期:2018-05-25
  • 通讯作者: 陈等 E-mail:chendeng2001@hotmail.com
  • 基金资助:
    RYBP下调cyclin D1的分子机制及其在肿瘤治疗中的作用

YAF2 promotes tumor cell proliferation via targeting cyclin D1 expression

  • Received:2018-03-02 Revised:2018-03-27 Online:2018-06-05 Published:2018-05-25

摘要: 目的 研究YY1相关因子2(YAF2)在肿瘤细胞中上调细胞周期蛋白D1(cyclin D1)表达的分子机制以及对肿瘤细胞增殖的影响。方法 在肿瘤细胞中过表达和敲低YAF2,用Western blot和实时荧光定量PCR实验检测YAF2和cyclin D1的表达;利用双荧光素酶报告基因实验探究YAF2对cyclin D1启动子活性的影响;流式细胞计量术分析YAF2对细胞周期的影响与cyclin D1表达的关系;平板克隆形成实验检测YAF2和cyclin D1不同表达水平对细胞增殖的影响。结果 YAF2上调cyclin D1的mRNA(P<0.05)和蛋白水平;YAF2激活cyclin D1的启动子(P<0.05);敲低YAF2通过调节cyclin D1使G0/G1期细胞比例增加(P<0.0001),S期细胞比例减少(P<0.002);YAF2通过靶向cyclin D1促进细胞克隆形成(P<0.05)。结论 在肿瘤细胞中,YAF2激活cyclin D1表达,促进肿瘤细胞周期进展和增殖。

关键词: 关键词:YAF2, 细胞周期蛋白 D1, 肿瘤细胞增殖

Abstract: Objective This study aims to explore the molecular mechanism by which YAF2 up-regulates cyclin D1 expression in tumor cells as well as the effect of YAF2-cyclin D1 regulatory loop on tumor cell proliferation. Methods Overexpression and knockdown experiments combined with Western blot and real-time quantitative PCR were used to detect the expressions of YAF2 and cyclin D1; Dual luciferase reporter assay was performed to investigate the effect of YAF2 on cyclin D1 promoter activity; Flow cytometry analysis was carried out to elucidate the effect of YAF2 on cell cycle progression through targeting cyclin D1; Colony formation assay was employed to determine cell proliferation under different YAF2 and cyclin D1 expression levels. Results YAF2 upregulates the expression of cyclin D1 at both the mRNA (P<0.05) and protein levels; YAF2 activates the promoter activity of cyclin D1 (P<0.05); YAF2 silencing increases the proportion of cells in G0/G1 phase (P<0.0001) and reduces the proportion of cells in S phase by regulating cyclin D1 (P<0.002); YAF2 facilitates the cell colony formation via targeting cyclin D1 (P<0.05). Conclusions In tumor cells, YAF2 promotes the expression of cyclin D1, and enhances cell cycle progression and cell proliferation.

Key words: Keyword: YAF2, Cyclin D1, Tumor cell proliferation