Huang Chen, Liu Li-Ying, Li Zong-Fang, Wang Pei, Ni Lei, Song Li-Ping, Xu De-Hui, Song Tu-Sheng
Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education/Department of Genetics and Molecular Biology, Medical School, Xi'an Jiaotong University, 205 Zhu Que Road, Xi'an, Shaanxi 710061, PR China.
Cell Biol Int. 2008 Sep;32(9):1081-90. doi: 10.1016/j.cellbi.2008.04.019. Epub 2008 May 2.
The mitogen activated protein kinases (MAPK) signaling cascade plays an important role in cell life. We proved that small interfering RNAs targeting MAPK1 (siRNA-2) could inhibit HeLa cell growth, but the effects of siRNA-2 on gene expression profile were unclear. Using Affymetrix GeneChip HG-U133A 2.0, we identified the long-term changes for 48 h in gene expression profile in HeLa cell treated by siRNA-2. The results showed that expressions of 181 genes were altered by siRNA-2 and were divided into two groups: (i) one group showed downregulation by siRNA-2, including the proliferation associated genes, small G protein, cytoskeleton associated protein and extracellular matrix associated protein; and (ii) the other group showed upregulation by siRNA-2, including interferon response genes, OAS family, TRIM family and apoptosis associated genes. The results of Real-time quantitative PCR for MAPK1, NUP188, P38, STAT1, STAT2, MPL and OAS1 were consistent with that of gene chip. Two networks were found to react substantially to the downregulation of MAPK1 by siRNA-2. One of the networks regulates cell growth through cell-cycle control, apoptosis and cytoskeleton. The other network is related to interferon-like response. Our findings suggest that siRNA-mediated downregulation of MAPK1 could be an attractive strategy for cancer therapy.
丝裂原活化蛋白激酶（MAPK）信号级联在细胞生命活动中发挥着重要作用。我们证实，靶向MAPK1的小干扰RNA（siRNA-2）能够抑制HeLa细胞生长，但siRNA-2对基因表达谱的影响尚不清楚。利用Affymetrix GeneChip HG-U133A 2.0芯片，我们鉴定了经siRNA-2处理的HeLa细胞在48小时内基因表达谱的长期变化。结果显示，181个基因的表达被siRNA-2改变，并分为两组：（i）一组基因表达被siRNA-2下调，包括增殖相关基因、小G蛋白、细胞骨架相关蛋白和细胞外基质相关蛋白；（ii）另一组基因表达被siRNA-2上调，包括干扰素反应基因、OAS家族、TRIM家族和凋亡相关基因。对MAPK1、NUP188、P38、STAT1、STAT2、MPL和OAS1进行实时定量PCR的结果与基因芯片结果一致。发现有两个网络对siRNA-2介导的MAPK1下调有显著反应。其中一个网络通过细胞周期调控、凋亡和细胞骨架来调节细胞生长。另一个网络与干扰素样反应有关。我们的研究结果表明，siRNA介导的MAPK1下调可能是一种有吸引力的癌症治疗策略。
