By immunohistochemical and a multivariate analysis, expressions of AEG-1 and MDM2 were elevated in glioma and high AEG-1 and MDM2 expressions were showed to be correlated with poor prognosis.
The miR-126 expression is abnormally low in glioma cells, and miR-126 inhibits the course of glioma through targeted regulation of PTEN/PI3K/Akt and MDM2-p53 pathways, which, therefore, can be used as a new potential biomarker for the diagnosis, treatment and prognosis of glioma.
To the best of our knowledge, the present study is the first to provide evidence suggesting that miR‑610 directly targets MDM2 proto-oncogene E3 ubiquitin protein ligase to function as a tumor suppressor in glioma.
These findings show that CDKN2 p16 540 C>G, CDKN2 p16 580 C>T and MDM2 SNP309 T>G variants and their haplotypes may be risk factors for the development of primary brain tumors, especially of glioma.
We also found no significant association between the MDM2 SNP309 polymorphism and glioma risk (pooled OR = 1.86, 95%CI = 0.94-3.67 and pooled OR = 1.25, 95%CI = 0.62-2.56, respectively) under the dominant and recessive models.
The polyarginine11R as a PTD, nuclear localization sequence (NLS), and laminin (Ln) fused to the p53 peptide corresponding to the MDM2 binding site (p53-NLS-Ln-11R) effectively penetrated the plasma membrane of the glioma cells and was translocated into the nucleus.
Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma.
Together, our findings suggest that p48 functions as an oncogene by promoting glioma tumorigenicity via interactions with HDM2 that contribute to p53 downregulation.
Immunohistochemical study of glioma tissues showed that the G/G genotype was associated with higher expression of MDM2 protein compared to the T/T genotype, suggesting that SNP309 attenuates MDM2 protein expression in vivo.
Although p53 accumulation appeared not to be important for the onset of cell death both in spheroid and biopsy cases, high levels of perinecrotic 60 kDa MDM2 may have implications for glioma cell death susceptibility in both p53 mutant and wild-type tumour cell populations.
In this study, we examined the effect of flavopiridol on a panel of glioma cell lines having different genetic profiles: five of six have codeletion of p16(INK4a) and p14(ARF); three of six have p53 mutations; and one of six shows overexpression of mouse double minute-2 (MDM2) protein.
It has been shown that the Hdmx gene is amplified in a subset of gliomas, but thus far, no data are available on HDMX protein expression in tumor cells.