Ren Wei, Lian Panfeng, Cheng Long, Du Peiyun, Guan Xin, Wang Hongyuan, Ding Lihua, Gao Zhenyang, Huang Xin, Xiao Fengjun, Wang Lisheng, Bi Xiaolin, Ye Qinong, Wang Enqun
Department of Stomatology, Anqing Municipal Hospital of Anhui Medical University, Anqing, Anhui 246003, P.R. China.
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, P.R. China.
Mol Med Rep. 2015 Sep;12(3):3958-3964. doi: 10.3892/mmr.2015.3844. Epub 2015 May 25.
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.
四半LIM结构域蛋白1(FHL1)已被确定为多种肿瘤中的肿瘤抑制因子。然而,FHL1在舌鳞状细胞癌(TSCC)中的生物学功能及潜在机制仍有待阐明。本研究表明,通过细胞增殖和软琼脂试验确定,FHL1在体外可抑制TSCC细胞的贴壁依赖性和非贴壁依赖性生长以及裸鼠体内肿瘤的生长。用FHL1小干扰RNA(siRNA)敲低FHL1可促进裸鼠体内肿瘤生长。机制上,流式细胞术分析表明,敲低FHL1可促进G1/S期细胞周期进程。此外,通过蛋白质印迹法和逆转录-定量聚合酶链反应检测细胞周期相关调节因子细胞周期蛋白D和细胞周期蛋白E的表达。在转染FHL1 siRNA的细胞中,细胞周期蛋白D和细胞周期蛋白E在蛋白质和mRNA水平均显著升高。这些结果表明,FHL1在TSCC中具有肿瘤抑制作用,且FHL1可能是TSCC基因治疗的一个有用靶点。