Upregulation of MAPK10, TUBB2B and RASL11B may contribute to the development of neuroblastoma

Mol Med Rep. 2019 Oct;20(4):3475-3486. doi: 10.3892/mmr.2019.10589. Epub 2019 Aug 20.

Abstract

The present study aimed to investigate genes and transcription factors (TFs) that may contribute to neuroblastoma (NB) development. The GSE78061 dataset that included 25 human NB cell lines and four retinal pigment epithelial cell lines was used to analyze differentially expressed genes (DEGs) between groups. Functional enrichment analysis and protein‑protein interaction (PPI) network analysis were performed for the identified DEGs. Additionally, submodule analysis and TF‑target regulatory networks were conducted. The relative mRNA expression levels of mitogen‑activated protein kinase 10 (MAPK10), tubulin β 2B class IIb (TUBB2B), RAS like family 11 member B (RASL11B) and integrin subunit α 2 (ITGA2) in the NB cell line SH‑SY5Y were compared with retinal pigment epithelial cell lines. A set of 386 upregulated and 542 downregulated DEGs were obtained. Upregulated DEGs were significantly associated with the 'neuron migration' and 'dopaminergic synapse signaling' pathways, whereas, downregulated DEGs were primarily involved in 'focal adhesion' such as ITGA2 and ITGA3. In the PPI networks analyzed, MAPK10, dopa decarboxylase (DDC), G protein subunit γ 2 (GNG2), paired like homeobox 2B (PHOX2B), TUBB2B, RASL11B, and ITGA2 were hub genes with high connectivity degrees. Additionally, PHOX2B was predicted to be a TF regulating TUBB2B in the regulatory network. The expressions of MAPK10, TUBB2B, RASL11B and ITGA2 were detected by reverse transcription‑quantitative polymerase chain reaction in the NB cell line SH‑SY5Y, and were consistent with the present bioinformatics results, suggesting that MAPK10, DDC, GNG2, PHOX2B, TUBB2B, RASL11B, ITGA2 and ITGA3 may contribute to NB development. Additionally, the present study identified a novel significant association between the increased expression levels of MAPK10, TUBB2B and RASL11B, and NB cells.

MeSH terms

  • Cell Line, Tumor
  • Databases, Nucleic Acid
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mitogen-Activated Protein Kinase 10 / biosynthesis*
  • Monomeric GTP-Binding Proteins / biosynthesis*
  • Neoplasm Proteins / biosynthesis*
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • Tubulin / biosynthesis*
  • Up-Regulation*

Substances

  • Neoplasm Proteins
  • TUBB2B protein, human
  • Tubulin
  • Mitogen-Activated Protein Kinase 10
  • Monomeric GTP-Binding Proteins
  • RASL11B protein, human