microRNA-2110 functions as an onco-suppressor in neuroblastoma by directly targeting Tsukushi

PLoS One. 2018 Dec 14;13(12):e0208777. doi: 10.1371/journal.pone.0208777. eCollection 2018.


microRNA-2110 (miR-2110) was previously identified as inducing neurite outgrowth in a neuroblastoma cell lines BE(2)-C, suggesting its differentiation-inducing and oncosuppressive function in neuroblastoma. In this study, we demonstrated that synthetic miR-2110 mimic had a generic effect on reducing cell survival in neuroblastoma cell lines with distinct genetic backgrounds, although the induction of cell differentiation traits varied between cell lines. In investigating the mechanisms underlying such functions of miR-2110, we identified that among its predicted target genes down-regulated by miR-2110, knockdown of Tsukushi (TSKU) expression showed the most potent effect in inducing cell differentiation and reducing cell survival, suggesting that TSKU protein plays a key role in mediating the functions of miR-2110. In investigating the clinical relevance of miR-2110 and TSKU expression in neuroblastoma patients, we found that low tumor miR-2110 levels were significantly correlated with high tumor TSKU mRNA levels, and that both low miR-2110 and high TSKU mRNA levels were significantly correlated with poor patient survival. These findings altogether support the oncosuppressive function of miR-2110 and suggest an important role for miR-2110 and its target TSKU in neuroblastoma tumorigenesis and in determining patient prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / metabolism
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Cell Survival / physiology
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • MicroRNAs / metabolism*
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism*
  • Neuroblastoma / mortality
  • Neuronal Outgrowth / physiology
  • Proteoglycans / genetics
  • Proteoglycans / metabolism*
  • RNA, Messenger / metabolism


  • Biomarkers, Tumor
  • Intercellular Signaling Peptides and Proteins
  • MIRN2110 microRNA, human
  • MicroRNAs
  • Proteoglycans
  • RNA, Messenger
  • TSKU protein, human