Zheng Jun-Nian, Sun Ya-Feng, Pei Dong-Sheng, Liu Jun-Jie, Ma Teng-Xiang, Han Rui-Fa, Li Wang, Zheng Dian-Bao, Chen Jia-Cun, Sun Xiao-Qing
Laboratory of Urology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
Acta Biochim Biophys Sin (Shanghai). 2006 Apr;38(4):254-61. doi: 10.1111/j.1745-7270.2006.00158.x.
Short hairpin RNAs (shRNAs) transcribed by RNA polymerase III promoters can trigger sequence-selective gene silencing in mammalian cells. By virtue of their excellent function in knocking down expression of cancer-associated genes, shRNAs could be used as new therapeutic agents for cancer. As overexpression of Ki67 in renal cancer has been correlated to a more aggressive tumor phenotype, inhibition of Ki67 protein expression by means of shRNAs seems to be a promising approach for the therapy of renal cancer. In this study, we constructed an expression plasmid encoding shRNAs against the Ki67 gene, named pSilencerKi67, and transfected it into human renal carcinoma cells. The pSilencerKi67 was shown to significantly knock down the expression of the Ki67 gene in human renal carcinoma cells, resulting in inhibiting proliferation and inducing apoptotic cell death that can be maintained for at least 6 d. These findings offer the promise of using vector-based shRNAs against Ki67 in renal cancer gene therapy.
由RNA聚合酶III启动子转录的短发夹RNA(shRNA)可在哺乳动物细胞中引发序列选择性基因沉默。凭借其在敲低癌症相关基因表达方面的出色功能,shRNA可作为癌症的新型治疗药物。由于肾癌中Ki67的过表达与更具侵袭性的肿瘤表型相关,通过shRNA抑制Ki67蛋白表达似乎是治疗肾癌的一种有前景的方法。在本研究中,我们构建了一个编码针对Ki67基因的shRNA的表达质粒,命名为pSilencerKi67,并将其转染到人肾癌细胞中。结果表明,pSilencerKi67可显著敲低人肾癌细胞中Ki67基因的表达,导致细胞增殖受到抑制并诱导凋亡性细胞死亡,且这种作用至少可持续6天。这些发现为在肾癌基因治疗中使用基于载体的针对Ki67的shRNA带来了希望。