Proteomic Profiling of Glioblastoma Cells following miR-21 Knockdown

摘要

Within 24h and 48h post-transfection of LNA-mir-21 we observe a significant increase of several tumor suppressive factors in addition to a concomitant decrease of oncogenic proteins. Within the tumor suppressive category are several proteins which are involved in p53 pathway activation in response to DNA damage. Upon activation of the p53 pathway several proteins increase/decrease as a result of the tumor suppressive p53 response; such proteins include up regulated AIFM1 and down regulated STMN1, observed upon miR-21 down regulation. We observe significant changes in the protein levels of U251 glioblastoma cells in response to miR-21 knockdown that reflect an activation of the DNA damage/p53 response of these cells, which in turn leads to an increase of pro-apoptotic (AIFM1) and decrease of anti-apoptotic/pro-proliferative (STMN1) protein. These changes in protein levels are consistent with the increased levels of apoptosis (Annexin-V) observed in 24h and 48h in the samples where miR-21 is knocked down. Identifying the proteomic changes in response to miR-21 knockdown will allow us to better understand the oncogenic mechanism of action of miR-21 in glioblastoma cells.