In the present study, we evaluated the expression of miR-145 and A Disintegrin and Metalloproteinase 19 (ADAM19) in glioblastoma multiforme (GBM) tissues and cells.
While restoration of microRNA-145 (miR-145) expression reduces chemoradioresistance in glioblastoma and suppress prostate cancer proliferation, migration and invasion, the role of miR-145 in response to radiation therapy for prostate cancer is still unknown.
The elevated miR-145 present in invasive glioblastoma cells (IM3 cells) targets and down-regulated srGAP1, thereby allowing downstream G-proteins to remain in their active state and promote the observed invasive phenotype.
The migration and invasion of malignant glioma cells into the surrounding normal brain tissues cause the poor outcome. miR-145, a miRNA found to be expressed in neurons, was recently found to have reduced expression in glioblastoma multiforme tumors.
In addition, a significantly favorable OS associated with upregulated miR-145 expression was observed in both squamous cell (SCC) (HR = 0.34, 95% CI 0.13 to 0.93) and glioblastoma (HR = 0.72, 95% CI 0.52 to 0.99).
Most importantly, higher hsa-miR-145 expression in GBM tumors yielded significantly better survival (p<0.005) in a subset of patients thus validating it as a genuine tumor suppressor miRNA.
Our study demonstrates that miR-145 has a tumor-suppressive function in glioblastoma in that it reduces proliferation, adhesion, and invasion of glioblastoma cells, apparently by suppressing the activity of oncogenic proteins Sox9 and ADD3.
In addition, we demonstrated a significant inhibition of invasion in silencing experiments with GB-NS shNEDD9 (shNEDD9), and an up-regulation of miR-145 in shNEDD9, suggesting a doublenegative feedback loop between miR-145 and NEDD9.