Whitson Jared M, Noonan Emily J, Pookot Deepa, Place Robert F, Dahiya Rajvir
University of California San Francisco, Department of Urology, San Francisco, CA 94121, USA.
Int J Cancer. 2009 Jul 15;125(2):446-52. doi: 10.1002/ijc.24370.
Small double stranded RNAs (dsRNA) are a new class of molecules which regulate gene expression. Accumulating data suggest that some dsRNA can function as tumor suppressors. Here, we report further evidence on the potential of dsRNA mediated p21 induction. Using the human renal cell carcinoma cell line A498, we found that dsRNA targeting the p21 promoter significantly induced the expression of p21 mRNA and protein levels. As a result, dsP21 transfected cells had a significant decrease in cell viability with a concomitant G1 arrest. We also observed a significant increase in apoptosis. These findings were associated with a significant decrease in survivin mRNA and protein levels. This is the first report that demonstrates dsRNA mediated gene activation in renal cell carcinoma and suggests that forced over-expression of p21 may lead to an increase in apoptosis through a survivin dependent mechanism.
小双链RNA(dsRNA)是一类新的调节基因表达的分子。越来越多的数据表明,一些dsRNA可作为肿瘤抑制因子发挥作用。在此,我们报告了关于dsRNA介导p21诱导潜力的进一步证据。使用人肾癌细胞系A498,我们发现靶向p21启动子的dsRNA显著诱导了p21 mRNA和蛋白质水平的表达。结果,转染dsP21的细胞活力显著降低,同时出现G1期阻滞。我们还观察到凋亡显著增加。这些发现与survivin mRNA和蛋白质水平的显著降低相关。这是第一份证明dsRNA在肾细胞癌中介导基因激活的报告,并表明p21的强制过度表达可能通过依赖survivin的机制导致凋亡增加。