RRC ID 52332
著者 Watanabe Y, Ishizuka Y, Hirano T, Nagasaki-Maeoka E, Hoshi R, Yoshizawa S, Uekusa S, Kawashima H, Sugito K, Shinohara K, Fukuda N, Nagase H, Soma M, Koshinaga T, Fujiwara K.
タイトル ZAR1 knockdown promotes the differentiation of human neuroblastoma cells by suppression of MYCN expression.
ジャーナル Med Oncol
Abstract Although DNA hypermethylation at non-promoter region of the Zygote arrest 1 (ZAR1) gene has been observed in many types of tumor, including neuroblastoma (NB), the role of this gene in tumor development and/or progression is unclear. One reason is that knowledge about the function of ZAR1 protein is limited. Although it has been reported that ZAR1 plays a crucial role in early embryogenesis and may act as a transcriptional repressor for some transcripts, the detailed mechanism is still elusive. In the present study, we analyzed public data of NB patients and found that higher expression levels of ZAR1 were significantly associated with a shorter survival period. Consistent with this result, ZAR1-depleted NB cells showed well-differentiated phenotypes with elongated neurites and upregulated expression of TRKA and RET, which are markers for differentiated NB. Moreover, the expression level of MYCN protein was markedly suppressed in ZAR1-depleted NB cells. MYCN-depleted cells showed similar phenotypes to ZAR1-depleted cells. The present findings indicate that ZAR1 has oncogenic effects in NB by suppressing cell differentiation via regulation of MYCN expression.
巻・号 34(9)
ページ 158
公開日 2017-8-8
DOI 10.1007/s12032-017-0999-x
PII 10.1007/s12032-017-0999-x
PMID 28791558
MeSH Cell Differentiation / genetics Egg Proteins / genetics* Egg Proteins / metabolism Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Kaplan-Meier Estimate N-Myc Proto-Oncogene Protein / genetics* Neurites / pathology Neuroblastoma / genetics* Neuroblastoma / mortality Neuroblastoma / pathology* Prognosis RNA, Small Interfering
IF 2.834
引用数 2
リソース情報
ヒト・動物細胞 NB9(RCB0477) NB-1(RCB1953)