Frankel Lisa B, Christoffersen Nanna R, Jacobsen Anders, Lindow Morten, Krogh Anders, Lund Anders H
Biotech Research and Innovation Centre, Bioinformatics Centre, University of Copenhagen, DK-2200 N Copenhagen, Denmark.
J Biol Chem. 2008 Jan 11;283(2):1026-33. doi: 10.1074/jbc.M707224200. Epub 2007 Nov 8.
MicroRNAs are emerging as important regulators of cancer-related processes. The miR-21 microRNA is overexpressed in a wide variety of cancers and has been causally linked to cellular proliferation, apoptosis, and migration. Inhibition of mir-21 in MCF-7 breast cancer cells causes reduced cell growth. Using array expression analysis of MCF-7 cells depleted of miR-21, we have identified mRNA targets of mir-21 and have shown a link between miR-21 and the p53 tumor suppressor protein. We furthermore found that the tumor suppressor protein Programmed Cell Death 4 (PDCD4) is regulated by miR-21 and demonstrated that PDCD4 is a functionally important target for miR-21 in breast cancer cells.
微小RNA正逐渐成为癌症相关进程的重要调节因子。微小RNA-21在多种癌症中均有过表达,并且与细胞增殖、凋亡及迁移存在因果关联。在MCF-7乳腺癌细胞中抑制微小RNA-21会导致细胞生长减缓。通过对缺失微小RNA-21的MCF-7细胞进行阵列表达分析,我们确定了微小RNA-21的mRNA靶标,并证明了微小RNA-21与p53肿瘤抑制蛋白之间存在联系。我们还发现肿瘤抑制蛋白程序性细胞死亡4(PDCD4)受微小RNA-21调控,并证明PDCD4是微小RNA-21在乳腺癌细胞中的一个功能重要靶标。