Human glioblastoma U251 (PTEN-mutant) and LN229 (PTEN wild-type) cells were treated with taxol and the miR-21 inhibitor (in a poly (amidoamine) (PAMAM) dendrimer), alone or in combination.
The serum miR-26a and miR-21 upregulation in glioblastoma patients compared to noncancerous controls and their downregulation in postoperative serum from glioblastoma patients suggest that these miRNAs could be used as serum-derived miRNA biomarkers for glioblastoma.
Our findings suggest that miR-21 represents a promising target for therapeutic manipulation to increase the efficacy of chemotherapeutic agents in treating glioblastoma, a highly lethal type of cancer.
Therefore, miRNA-21 in the plasma may be used as a novel diagnostic biomarker to distinguish patients with PCNSL from those with glioblastoma, whereas miRNA-21 in the CSF may have potential as a predictor of chemotherapeutic effect in PCNSL.
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.
We hypothesized that PLGA nanoparticles carrying antisense miR-21 to glioblastoma cells might beneficially knock down endogenous miR-21 prior to TMZ treatment.
Furthermore, we demonstrate that miR-30b/c and miR-21 target respectively the 3' untranslated region of caspase-3 and TAp63 mRNAs, and that those proteins mediate some of the effects of miR-30 and -21 on TRAIL resistance, even in human glioblastoma primary cells and in lung cancer cells.
Gene set enrichment analysis on averaged ProMISe uniquely revealed respective target enrichments of oncomirs miR-21 and 145 in glioblastoma and ovarian cancers.
Taken together, these findings suggest that miR-21 inhibitor can increase IR-induced growth arrest and apoptosis in U251 glioblastoma cells, at least in part by abrogating G(2)-M arrest, and that Cdc25A is a potential target of miR-21.
This review will focus on the roles of miRNAs family members (particularly miR-21 and its target gene PDCD4) in tumors like glioblastoma and new targeting strategies, as examples some new targeting therapeutic methods and molecular mechanisms of signal pathways in glioblastoma therapeutics, to give the reader the current trends of approach to target regulation of these miRNA and genes for future glioma therapies.
Our results identify IGFBP3 as a novel miR-21 target gene in glioblastoma and suggest that the oncogenic miRNA miR-21 down-regulates the expression of IGFBP3, which acts as a tumor suppressor in human glioblastoma.