Downregulation of N‑Myc inhibits neuroblastoma cell growth via the Wnt/β‑catenin signaling pathway

Wang,Yingge; Gao,Shan; Wang,Weiguang; Xia,Yuting; Liang,Jingyan

doi:10.3892/mmr.2018.8966

Downregulation of N‑Myc inhibits neuroblastoma cell growth via the Wnt/β‑catenin signaling pathway

Authors:
- Yingge Wang
- Shan Gao
- Weiguang Wang
- Yuting Xia
- Jingyan Liang
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Affiliations: Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Neurology, Shanghai JiaoTong University Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, P.R. China, Department of Hematology, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154003, P.R. China, Research Center for Vascular Biology, College of Medicine, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
Published online on: May 3, 2018 https://doi.org/10.3892/mmr.2018.8966
Pages: 377-384

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Abstract

Neuroblastoma, one of the most common types of cancer in childhood, is commonly treated with surgery, radiation and chemotherapy. However, prognosis and survival remain poor for children with high‑risk neuroblastoma. Therefore, the identification of novel, effective therapeutic targets is necessary. N‑Myc, a proto‑oncogene protein encoded by the v‑myc avial myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) gene, is associated with tumorigenesis. In the present study, the effect of N‑Myc silencing on MYCN‑amplified CHP134 and BE‑2C neuroblastoma cells was evaluated, and the underlying molecular mechanism was investigated. N‑Myc was successfully knocked down using an N‑Myc‑specific small interfering RNA, the efficacy of interference efficiency confirmed by reverse transcription‑quantitative polymerase chain reaction and western blotting. Cell viability was evaluated by MTT assay and apoptosis was measured by ELISA assay. The results indicated that MYCN silencing significantly decreased cell viability and promoted apoptosis. Subsequently, the expression levels of key Wnt/β‑catenin signaling pathway proteins were detected by western blotting, and MYCN silencing was demonstrated to inhibit Wnt/β‑catenin signaling, decreasing the expression ofanti‑apoptosis proteins and increasing the expression of pro‑apoptosis protein. This suggested that N‑Myc regulated survival and growth of CHP134 and BE‑2C neuroblastoma cells, potentially through Wnt/β‑catenin signaling. Furthermore, associated proteins, N‑Myc and STAT interactor and dickkopf Wnt signaling pathway inhibitor 1, were demonstrated to be involved in this regulation. Therefore, N‑Myc and its downstream targets may provide novel therapeutic targets for the treatment of neuroblastoma.

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