miR-21 may regulate the proliferation and apoptosis of human glioma cells by downregulating the expression of the PTEN protein, and miR-21 may represent a potential therapeutic target for the treatment of glioma.
Then, we also analyzed the impact of TERT promoter mutations, PTEN deletion, EGFR amplification and MGMT promoter methylation in diagnosis, prognosis and response to therapy in glioma molecular subgroup.
We modified an immune-competent, genetically-driven mouse glioma model (forced PDGF expression + PTEN loss) where a portion of the tumor burden is irradiated (PDGF) and another un-irradiated luciferase expressing tumor (PDGF+Luciferase) is used as a readout of the abscopal effect following systemic anti-PD-L1 immunotherapy.
We did whole exome sequencing for 11 GBM-PN cases and found that the percentage of TP53, PIK3CA, PIK3R1, or PTEN mutation in our GBM-PN cases (72.7%, 27.3%, 27.3%, and 27.3% respectively) was much higher than that in cases in TCGA GBM 2008, TCGA GBM 2013, and TCGA lower-grade glioma databases.
Among the many possible mechanisms underlying its pathogenesis, hyperactivation of the PI3K/Akt pathway is essential to the occurrence and development of glioma through the loss of PTEN or somatic activating mutations in PIK3CA.
Through comparative analyses of 286 cases of IDH-wildtype and IDH-mutant lower-grade glioma from a TCGA data set, we report that IDH-mutant gliomas have increased expression of tumor-suppressor genes (NF1, PTEN, and PIK3R1) and decreased expression of oncogenes(AKT2, ARAF, ERBB2, FGFR3, and PDGFRB) and glioma progression genes (FOXM1, IGFBP2, and WWTR1) compared with IDH-wildtype gliomas.
As expected, luciferase results verified the putative target site and also revealed the complementary binding between miR-19a and MEG3. miR-19a represses the expression of PTEN and promotes glioma cell proliferation, migration, and invasion.
In the current study, we show that co-expression of PIKE-A and CDK4 in TP53/PTEN double knockout GBM mouse model additively shortens the latency of glioma onset and survival compared to overexpression of these genes alone.