Tao Jiang, Tao Suxiong, Han Junli, Zhou Zhuojun, Zhang Xiaoping, Wang Haining, Chen Rongjing, Ji Fang, Zhu Yaqin
Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
Cell Physiol Biochem. 2014;33(5):1579-90. doi: 10.1159/000358721. Epub 2014 May 16.
BACKGROUND/AIMS: RECQL1, a member of the human RECQ helicase family, participates in DNA repair. Recent reports showed that RECQL1 silencing in cancer cells resulted in mitotic catastrophe, which prevented tumor growth in murine models. However, its therapeutic potential has never been examined in tongue squamous cell carcinoma (SCC).
To explore the role of RECQL1 in the development of tongue SCC, we used RNA interference technology to silence RECQL1 in SCC-9 and SCC-15 human tongue SCC cell lines, and to subsequently evaluate its effects both in vitro and in vivo.
After RECQL1 was silenced in SCC cells by siRNA, we observed downregulation of RECQL1 mRNA and protein in cancer cells. RECQL1 is one of the predicted miR-203 targets, and we found that miR-203 downregulated the expression of RECQL1 at the post-transcriptional level. RECQL1-shRNA or miR-203 overexpression inhibited SCC-9 cell growth. In addition, there was accumulation of cells in the sub-G1 fraction and increased apoptosis 72 h post-transfection. In addition, knockdown of RECQL1 led to a strong anticancer effect, as the tumorigenicity of SCC-9 cells was inhibited in vivo. Moreover, we found that two immunosuppressive factors were also significantly downregulated upon RECQL1 knockdown or miR-203 overexpression in vitro.
Collectively, these results indicate that RECQL1 plays an important regulatory role in cancer cell proliferation and tumor progression.
背景/目的：RECQ1是人类RECQ解旋酶家族的成员之一，参与DNA修复。最近的报道显示，癌细胞中RECQ1基因沉默会导致有丝分裂灾难，从而抑制小鼠模型中的肿瘤生长。然而，其在舌鳞状细胞癌（SCC）中的治疗潜力尚未得到研究。
为了探究RECQ1在舌SCC发生发展中的作用，我们利用RNA干扰技术使SCC-9和SCC-15人舌SCC细胞系中的RECQ1基因沉默，随后评估其在体外和体内的作用效果。
通过小干扰RNA（siRNA）使SCC细胞中的RECQ1基因沉默后，我们观察到癌细胞中RECQ1信使核糖核酸（mRNA）和蛋白表达下调。RECQ1是预测的微小核糖核酸-203（miR-203）靶点之一，我们发现miR-203在转录后水平下调RECQ1的表达。RECQ1短发夹RNA（shRNA）或miR-203过表达抑制SCC-9细胞生长。此外，转染后72小时，亚G1期细胞出现积聚且细胞凋亡增加。另外，RECQ1基因敲低具有显著的抗癌作用，因为SCC-9细胞的致瘤性在体内受到抑制。而且，我们发现体外RECQ1基因敲低或miR-203过表达后，两种免疫抑制因子也显著下调。
总体而言，这些结果表明RECQ1在癌细胞增殖和肿瘤进展中发挥重要的调节作用。
