MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells

Abstract

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-

Apoptosis and the target genes of microRNA-21

“…Target genes shown in green are specific to apoptosis with other targets shown in purple. miR-21 is a negative regulator of p53 signaling[9], and NF-κB signaling is promoted by miR-21[10]. p53 inactivation and NF-κB activation are implicated in deregulation of glucose flux and oxidative phosphorylation[11].…”

“…When miR-21 is inhibited in glioblastoma cells, an Hnrpk-dependent repression of growth and an increase in apoptosis and cell cycle arrest are observed[9]. Hnrpk is also involved in the regulation of transcription and translation, forming complexes with Tbp or Sp1 to enhance the transcription of c-Myc and c-Src, respectively.…”

“…The inhibition of TAp63 is associated with chemoresistance. When miR-21 is inhibited in glioblastoma cells, TAp63-dependent repression of growth, an increase in apoptosis and cell cycle arrest are observed[9],[41].…”

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics

“…Antiapoptotic miRNAs target proapoptotic genes and are frequently upregulated with GBM. miR‐21 is antiapoptotic and enhances tumor formation by targeting the signaling pathways of P53 and TGF‐ β as well as the mitochondrial apoptotic pathway 46. Inhibition of miR‐21 results in activation of caspases, suspension of cell growth, reduced invasion, increased apoptosis, and enhanced chemosensitivity.…”

“…Inhibition of miR‐21 results in activation of caspases, suspension of cell growth, reduced invasion, increased apoptosis, and enhanced chemosensitivity. These effects are mediated in part by decreased repression of targets including HNRPK, TAP63 , and PDCD4 37, 44, 46. Further, miR‐21 can modulate the extrinsic apoptotic pathway through downregulation of FASL , an ability that has been particularly evident in cancer stem cells 47.…”