MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells.
MicroRNA dysregulation is observed in different types of cancer. MiR-21 up-regulation has been reported for the majority of cancers profiled to date; however, knowledge is limited on the mechanism of action of miR-21, including identification of functionally important targets that contribute to its proproliferative and antiapoptotic actions. In this study, we show for the first time that miR-21 targets multiple important components of the p53, transforming growth factor-beta (TGF-beta), and mitochondrial apoptosis tumor-suppressive pathways. Down-regulation of miR-21 in glioblastoma cells leads to derepression of these pathways, causing repression of growth, increased apoptosis, and cell cycle arrest. These phenotypes are dependent on two of the miR-21 targets validated in this study, HNRPK and TAp63. These findings establish miR-21 as an important oncogene that targets a network of p53, TGF-beta, and mitochondrial apoptosis tumor suppressor genes in glioblastoma cells.
Papagiannakopoulos
Thales
T
Department of Molecular, Cellular and Developmental Biology, Neuroscience Research Institute, University of California, Santa Barbara, California 93106, USA.
Shapiro
Alice
A
Kosik
Kenneth S
KS
D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000502:physiology; D018390:Gene Targeting; D050259:Genes, Mitochondrial / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*; D008954:Models, Biological; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D014407:Tumor Cells, Cultured
C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta