FHL1 inhibits the growth of tongue squamous cell carcinoma cells via Gl/S cell cycle arrest
FHL1 inhibits the growth of tongue squamous cell carcinoma cells via Gl/S cell cycle arrest
复制标题
FHL1 通过 G1/S 细胞周期阻滞抑制舌鳞状细胞癌细胞的生长。
DOI：
10.3892/mmr.2015.3844
复制
发表时间：
2015-09-01
影响因子：
3.4
通讯作者：
Wang, Enqun
中科院分区：
文献类型：
--
作者：
Ren, Wei;Lian, Panfeng;Wang, Enqun
4.5LIM蛋白1(FHL1)在多种类型的肿瘤中被认为是一种肿瘤抑制因子。然而，FHL1在舌鳞状细胞癌(TSCC)中的生物学作用及其机制尚不清楚。本研究通过细胞增殖和软琼脂实验证明，FHL1在体外抑制TSCC细胞的贴壁依赖性和非贴壁性生长，并抑制裸鼠肿瘤的生长。用FHL1小干扰RNA(SiRNA)敲除FHL1可促进裸鼠肿瘤生长。从机制上讲，流式细胞仪分析表明FHL1基因敲除促进了G1/S细胞周期的进展。用Western blotting和逆转录定量聚合酶链式反应检测细胞周期相关调控因子细胞周期蛋白D和细胞周期蛋白E的表达。在FHL1 siRNA转染细胞中，细胞周期蛋白D和细胞周期蛋白E在蛋白和mRNA水平均显著升高。这些结果表明，FHL1在TSCC中具有抑瘤作用，FHL1可能是TSCC基因治疗的有用靶点。
Four and a half LIM protein 1 (FHL1) has been characterized as a tumor suppressor in various types of tumor. However, the biological function and underlying mechanism of FHL1 in tongue squamous cell carcinoma (TSCC) remain to be elucidated. The present study demonstrated that FHL1 inhibits anchorage‑dependent and ‑independent growth of TSCC cells in vitro and tumor growth in nude mice, as determined by cell proliferation and soft agar assays. Knockdown of FHL1 with FHL1 small interfering RNA (siRNA) promoted tumor growth in nude mice. Mechanistically, flow cytometric analysis showed that knockdown of FHL1 promoted G1/S cell cycle progression. Furthermore, expression of cell cycle‑associated regulators, cyclin D and cyclin E, were detected by western blotting and reverse transcription‑quantitative polymerase chain reaction. Cyclin D and cyclin E were markedly elevated at both the protein and mRNA level in the FHL1 siRNA‑transfected cells. These results suggested that FHL1 has a tumor suppressive role in TSCC and that FHL1 may be a useful target for TSCC gene therapy.