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:C0027819 (
neuroblastoma
)
27,800
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Derangement of cellular differentiation because of mutation or inappropriate expression of specific genes is a common feature in tumors. Here, we show that the expression of
ZNF281
, a zinc finger factor involved in several cellular processes, decreases during terminal differentiation of murine cortical neurons and in retinoic acid-induced differentiation of
neuroblastoma
(NB) cells. The ectopic expression of
ZNF281
inhibits the neuronal differentiation of murine cortical neurons and NB cells, whereas its silencing causes the opposite effect. Furthermore, TAp73 inhibits the expression of
ZNF281
through miR34a. Conversely, MYCN promotes the expression of
ZNF281
at least in part by inhibiting miR34a. These findings imply a functional network that includes p73, MYCN, and
ZNF281
in NB cells, where
ZNF281
acts by negatively affecting neuronal differentiation. Array analysis of NB cells silenced for
ZNF281
expression identified GDNF and NRP2 as two transcriptional targets inhibited by
ZNF281
. Binding of
ZNF281
to the promoters of these genes suggests a direct mechanism of repression. Bioinformatic analysis of NB datasets indicates that
ZNF281
expression is higher in aggressive, undifferentiated stage 4 than in localized stage 1 tumors supporting a central role of
ZNF281
in affecting the differentiation of NB. Furthermore, patients with NB with high expression of
ZNF281
have a poor clinical outcome compared with low-expressors. These observations suggest that
ZNF281
is a controller of neuronal differentiation that should be evaluated as a prognostic marker in NB.
...
PMID:ZNF281 inhibits neuronal differentiation and is a prognostic marker for neuroblastoma. 2994 55
