The MDM2 and MDMX oncogenes are overexpressed in various types of human cancer and are highly associated with the initiation, progression, metastasis and chemotherapeutic resistance of these diseases, including prostate cancer.
This study is the first, to our knowledge, to demonstrate regulation of the MDM4rs4245739 SNP C-allele by two miRNAs in prostate cancer, and thereby to identify a mechanism by which the MDM4rs4245739 SNP A-allele may be associated with an increased risk for prostate cancer.
We conclude, MDM4 SNP34091 status to be associated with reduced risk of breast cancer, in particular in individuals carrying the MDM2 SNP309GG genotype, but not to be associated with either lung-, colon- or prostate cancer.
The deubiquitinating enzyme USP2a has shown oncogenic properties in many cancer types by impairing ubiquitination of FASN, MDM2, MDMX or Aurora A. Aberrant expression of USP2a has been linked to progression of human tumors, particularly prostate cancer.
Previously, we described that MDR phenotype in PCa could be related with high basal and drug-induced expression of MDR proteins P-Glycoprotein (P-Gp), MRP1, and LRP.
Both the Mdm4 and Hausp SNPs (rs1380576 and rs1529916) were found to be associated with higher D'Amico risk prostate cancer category at the time of diagnosis (P = 0.023 and P = 0.046, respectively).
These results provide the first mechanistic link between expression of MRP1 and mutation of p53 in human prostate cancer and support recent clinical associations.