Downregulation of FOXP1 Inhibits Cell Proliferation in Hepatocellular Carcinoma by Inducing G1/S Phase Cell Cycle Arrest.
Downregulation of FOXP1 Inhibits Cell Proliferation in Hepatocellular Carcinoma by Inducing G1/S Phase Cell Cycle Arrest.
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FOXP1 下调通过诱导 G1/S 期细胞周期停滞抑制肝细胞癌中的细胞增殖
DOI：
10.3390/ijms17091501
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发表时间：
2016-09-08
影响因子：
5.6
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Wang X;Sun J;Cui M;Zhao F;Ge C;Chen T;Yao M;Li J
叉头盒P1（FOXP 1）属于翼螺旋转录因子家族，其参与细胞增殖、分化、代谢和寿命的过程。FOXP 1在体外可影响肝癌细胞的增殖和迁移能力。然而，FOXP 1在肝癌细胞增殖中的作用机制尚不清楚。本研究旨在进一步探讨FOXP 1在肝癌细胞增殖中的作用及其相关机制。通过Western印迹分析、肿瘤异种移植模型和流式细胞术分析来阐明FOXP 1在人HCC细胞增殖调节中的功能。我们观察到沉默FOXP 1在体外和体内均显著抑制HCC细胞的生长能力。此外，敲低FOXP 1诱导G1/S期阻滞，总Rb和磷酸化Rb（活性型）的表达以及E2 F1的水平在24 h时显著降低，但其他蛋白，包括细胞周期蛋白依赖性激酶（CDK）4和6和细胞周期蛋白D1没有显示出明显的变化。总之，FOXP 1的下调通过诱导G1/S期细胞周期阻滞来抑制肝癌细胞的增殖，并且磷酸化Rb的减少是这种G1/S期阻滞的主要贡献者。
Forkhead box P1 (FOXP1) belongs to a family of winged-helix transcription factors that are involved in the processes of cellular proliferation, differentiation, metabolism, and longevity. FOXP1 can affect cell proliferation and migratory ability in hepatocellular carcinoma (HCC) in vitro. However, little is known about the mechanism of FOXP1 in the proliferation of HCC cells. This study aimed to further explore the function of FOXP1 on the proliferation of HCC cells as well as the relevant mechanism involved. Western blot analysis, tumor xenograft models, and flow cytometry analysis were performed to elucidate the function of FOXP1 in the regulation of cell proliferation in human HCC. We observed that silencing FOXP1 significantly suppressed the growth ability of HCC cells both in vitro and in vivo. In addition, knockdown of FOXP1 induced G1/S phase arrest, and the expression of total and phosphorylated Rb (active type) as well as the levels of E2F1 were markedly decreased at 24 h; however, other proteins, including cyclin-dependent kinase (CDK) 4 and 6 and cyclin D1 did not show noticeable changes. In conclusion, downregulation of FOXP1 inhibits cell proliferation in hepatocellular carcinoma by inducing G1/S phase cell cycle arrest, and the decrease in phosphorylated Rb is the main contributor to this G1/S phase arrest.
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