Effects of small interfering RNAs targeting MAPK1 on gene expression profile in HeLa cells as revealed by microarray analysis.
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.
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. hchen@mail.xjtu.edu.cn
Chen
C
Huang
Li-Ying
LY
Liu
Zong-Fang
ZF
Li
Pei
P
Wang
Lei
L
Ni
Li-Ping
LP
Song
De-Hui
DH
Xu
Tu-Sheng
TS
Song
D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors*; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
D034741:RNA, Small Interfering; D019950:Mitogen-Activated Protein Kinase 1