Laboratory of Oncoendocrinology, N.N.Petrov Institute of Oncology, Pesochny-2, St Petersburg, Russia.
Cancer Gene Ther. 2013 May;20(5):326-9. doi: 10.1038/cgt.2013.20. Epub 2013 Apr 26.
Therapeutic gene silencing is a promising approach for treatment of cancer. Despite substantial efforts, however, only few such therapeutic methods have been clinically tested. The heterogeneity in gene expression profiles among malignant tissues and the dynamic control of gene expression in individual tumors makes identifying universal and effective targets a challenge. Further development of gene silencing therapy requires new approaches to comprehend and manage gene expression in cancer cells. In this study, we proposed and evaluated experimentally a new approach to design multi-gene silencing therapy. Using a simplified model of gene expression control, we show that genes commonly regulated by the same microRNA represent optimal combinations of targets for small hairpin RNA/small interfering RNA-based gene silencing. The proposed method of target gene selection and co-silencing can be explored as an algorithm for personalized cancer gene therapy.
治疗性基因沉默是治疗癌症的一种很有前途的方法。然而，尽管付出了巨大的努力，只有少数这样的治疗方法经过了临床测试。恶性组织中基因表达谱的异质性和个体肿瘤中基因表达的动态控制使得确定普遍有效的靶点成为一项挑战。基因沉默治疗的进一步发展需要新的方法来理解和管理癌细胞中的基因表达。在这项研究中，我们提出并实验评估了一种新的设计多基因沉默治疗的方法。使用基因表达控制的简化模型，我们表明，通常受同一 microRNA 调控的基因是小发夹 RNA/小干扰 RNA 基因为基因沉默的最佳靶点组合。所提出的靶基因选择和共沉默的方法可以作为个性化癌症基因治疗的算法进行探索。
