RECQL1 Plays an Important Role in the Development of Tongue Squamous Cell Carcinoma
RECQL1 Plays an Important Role in the Development of Tongue Squamous Cell Carcinoma
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RECQL1在舌鳞状细胞癌的发展中发挥重要作用
DOI：
10.1159/000358721
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发表时间：
2014-01-01
影响因子：
--
通讯作者：
Zhu, Yaqin
中科院分区：
文献类型：
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作者：
Tao, Jiang;Tao, Suxiong;Zhu, Yaqin
背景/目的：RECQL 1是人RECQ解旋酶家族的成员，参与DNA修复。最近的报道表明，RECQL 1在癌细胞中的沉默导致有丝分裂灾难，这阻止了小鼠模型中的肿瘤生长。然而，它的治疗潜力从来没有检查舌鳞状细胞癌（SCC）。研究方法：为了探讨RECQL 1在舌鳞癌发生发展中的作用，我们采用RNA干扰技术沉默人舌鳞癌细胞系SCC-9和SCC-15中的RECQL 1，并随后评估其在体外和体内的作用。结果：通过siRNA沉默SCC细胞中RECQL 1后，癌细胞中RECQL 1 mRNA和蛋白表达下调。RECQL 1是miR-203预测的靶点之一，我们发现miR-203在转录后水平下调RECQL 1的表达。RECQL 1-shRNA或miR-203过表达抑制SCC-9细胞生长。此外，在转染后72小时，亚G1级分中存在细胞积累并且细胞凋亡增加。此外，RECQL 1的敲低导致强的抗癌作用，因为SCC-9细胞的致瘤性在体内被抑制。此外，我们发现两种免疫抑制因子在RECQL 1敲低或miR-203过表达时也显著下调。结论：RECQL 1在肿瘤细胞增殖和肿瘤进展中起着重要的调控作用。
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). Methods: 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. Results: 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. Conclusion: Collectively, these results indicate that RECQL1 plays an important regulatory role in cancer cell proliferation and tumor progression.