Open Access
ARTICLE
MYCN Directly Targets NeuroD1 to Promote Cellular Proliferation in Neuroblastoma
Fangjin Lu*, Bin Mu†, Ge Jin*, Lin Zhu‡, Ping Mu§
* Department of Pharmacology, Shenyang Medical College, Shenyang, P.R. China
† Shanghai Zhaohui Pharmaceutical Co. Ltd., Shanghai, P.R. China
‡ Department of Biochemistry and Molecular Biology, Shenyang Medical College, Shenyang, P.R. China
§ Department of Physiology, Shenyang Medical College, Shenyang, P.R. China
Oncology Research 2021, 29(1), 1-10. https://doi.org/10.3727/096504021X16401852341873
Abstract
NeuroD1 is a neuronal differentiation factor that contains a basic helix–loop–helix (bHLH) motif. Recently,
NeuroD1 was found to be associated with tumorigenesis in neuroblastoma (NB) and is known to promote cell
proliferation and migration in these cells. Here we found that MYCN regulates the expression of NeuroD1 in
NB cells and that the downregulation of MYCN using short hairpin RNAs (shRNA) results in the inhibition
of cellular proliferation in NB cells. Moreover, the phenotype induced by MYCN shRNA was rescued by
the exogenous expression of NeuroD1. Chromatin immunoprecipitation (ChIP) assay showed that MYCN
directly binds to the E-box element in the NeuroD1 promoter region. In addition, our evaluation of two clinical databases showed that there was a positive correlation between the expression of MYCN and NeuroD1 in
NB patients, which supports our in vitro data. In conclusion, this study demonstrates that MYCN-regulated
NeuroD1 expression is one of the important mechanisms underlying enhanced cellular proliferation induced
by the increase in MYCN expression in NB, and our results provide an important therapeutic target for NB in
the future.
Keywords
Cite This Article
Lu, F., Mu, B., Jin, G., Zhu, L., Mu, P. (2021). MYCN Directly Targets NeuroD1 to Promote Cellular Proliferation in Neuroblastoma.
Oncology Research: Featuring Preclinical and Clinical Cancer Therapeutics, 29(1), 1–10.