Neuroblastoma is the most common extracranial solid
tumor of childhood, and accounts for ∼15% of
all childhood cancer deaths. The
histone demethylase,
lysine-specific demethylase 1 (KDM1A, previously known as LSD1), is strongly expressed in
neuroblastomas, and overexpression correlates with poor patient prognosis. Inducing differentiation in
neuroblastoma cells has previously been shown to down regulate KDM1A, and
siRNA-mediated KDM1A knockdown inhibited
neuroblastoma cell viability. The
microRNA, miR-137, has been reported to be downregulated in several human
cancers, and KDM1A
mRNA was reported as a putative target of miR-137 in
colon cancer. We hypothesized that miR-137 might have a
tumor-suppressive role in
neuroblastoma mediated via downregulation of KDM1A. Indeed, low levels of miR-137 expression in primary
neuroblastomas correlated with poor patient prognosis. Re-expressing miR-137 in
neuroblastoma cell lines increased apoptosis and decreased cell viability and proliferation. KDM1A
mRNA was repressed by miR-137 in
neuroblastoma cells, and was validated as a direct target of miR-137 using reporter assays in SHEP and HEK293 cells. Furthermore,
siRNA-mediated KDM1A knockdown phenocopied the miR-137 re-expression phenotype in
neuroblastoma cells. We conclude that miR-137 directly targets KDM1A
mRNA in
neuroblastoma cells, and activates cell properties consistent with
tumor suppression. Therapeutic strategies to re-express miR-137 in
neuroblastomas could be useful to reduce
tumor aggressiveness.