Sept. 2008 | Galina Gabriely, Thomas Wurdinger, Santosh Kesari, Christine C. Esau, Julja Burchard, Peter S. Linsley, and Anna M. Krichevsky
This study investigates the role of microRNA 21 (miR-21) in glioma invasion and its potential as a therapeutic target. MiR-21 is significantly upregulated in glioblastoma (GBM) and other cancers, and has been implicated in various carcinogenic processes. The authors demonstrate that miR-21 regulates multiple genes associated with glioma cell apoptosis, migration, and invasiveness, including RECK and TIMP3, which are inhibitors of matrix metalloproteinases (MMPs). Inhibition of miR-21 using antisense oligonucleotides leads to increased levels of RECK and TIMP3, reduced MMP activities, and decreased migratory and invasive abilities of glioma cells in vitro and in a human glioma model in nude mice. The results suggest that miR-21 contributes to glioma malignancy by downregulating MMP inhibitors, leading to increased MMP activity and cancer cell invasiveness. The study also indicates that inhibiting a single oncomir like miR-21 with specific antisense molecules can provide a novel therapeutic approach to modulate multiple proteins whose expression is deregulated in cancer.This study investigates the role of microRNA 21 (miR-21) in glioma invasion and its potential as a therapeutic target. MiR-21 is significantly upregulated in glioblastoma (GBM) and other cancers, and has been implicated in various carcinogenic processes. The authors demonstrate that miR-21 regulates multiple genes associated with glioma cell apoptosis, migration, and invasiveness, including RECK and TIMP3, which are inhibitors of matrix metalloproteinases (MMPs). Inhibition of miR-21 using antisense oligonucleotides leads to increased levels of RECK and TIMP3, reduced MMP activities, and decreased migratory and invasive abilities of glioma cells in vitro and in a human glioma model in nude mice. The results suggest that miR-21 contributes to glioma malignancy by downregulating MMP inhibitors, leading to increased MMP activity and cancer cell invasiveness. The study also indicates that inhibiting a single oncomir like miR-21 with specific antisense molecules can provide a novel therapeutic approach to modulate multiple proteins whose expression is deregulated in cancer.