Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0017638 (
glioma
)
30,880
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Despite extensive investigation into the role of let-7 miRNAs in pathological tumor processes, their involvement in the DNA damage response remains unclear. Here we show that most let-7 family members down-regulate MDM4 expression via binding to MDM4 mRNA at a conserved DNA sequence. Expression of exogenous let-7 miRNA mimics decreased
MDM4 protein
but not mRNA levels. Several DNA damage reagents increased let-7 expression, thereby decreasing
MDM4 protein
levels in
glioma
cells. Inhibition of endogenous let-7 with antisense RNAs rescued
MDM4 protein
levels with or without MG132, a proteasome-dependent degradation inhibitor. An MDM4 mutation identified in a
glioma
patient was associated with loss of the putative MDM4 target site. Therefore, let-7 binding to MDM4 is implicated in the DNA damage response.
...
PMID:MDM4 regulation by the let-7 miRNA family in the DNA damage response of glioma cells. 2602 11
