Song Jun, Pang Shen, Lu Yingchun, Yokoyama Kazunari K, Zheng Jun-Ying, Chiu Robert
Dental Research Institute, University of California Los Angeles (UCLA) School of Dentistry, UCLA, Los Angeles, California 90095, USA.
Cancer Res. 2004 Nov 1;64(21):7661-3. doi: 10.1158/0008-5472.CAN-04-1751.
The success of gene therapy using a RNA interference approach relies on small interfering RNA (siRNA) expression from a highly tissue-specific RNA polymerase II promoter rather than from ubiquitous RNA polymerase III. Accordingly, we have developed a prostate-specific vector that expresses siRNAs from the human prostate-specific antigen promoter, a RNA polymerase II promoter. Our data demonstrate androgen-dependent and tissue-specific siRNA-mediated gene silencing in the androgen-responsive prostate cancer cell line, LNCaP. The biological significance was evidenced by altered apoptotic activity through the inhibition of the apoptosis-related regulatory gene. These results demonstrate that siRNA-mediated gene silencing from a tissue-specific RNA polymerase II promoter could be a potential tool for tissue-specific gene therapy.
使用RNA干扰方法的基因治疗的成功依赖于从高度组织特异性的RNA聚合酶II启动子而非普遍存在的RNA聚合酶III表达小干扰RNA（siRNA）。因此，我们开发了一种前列腺特异性载体，其从人前列腺特异性抗原启动子（一种RNA聚合酶II启动子）表达siRNA。我们的数据证明了在雄激素反应性前列腺癌细胞系LNCaP中雄激素依赖性和组织特异性的siRNA介导的基因沉默。通过抑制凋亡相关调节基因改变凋亡活性证明了其生物学意义。这些结果表明，从组织特异性RNA聚合酶II启动子进行siRNA介导的基因沉默可能是组织特异性基因治疗的一种潜在工具。
