microRNA-2110 Functions as an Onco-suppressor in Neuroblastoma by Directly Targeting Tsukushi
Date
2018-12
Authors
Zhao, Zhenze
Partridge, Veronica
Sousares, Michaela
Shelton, Spencer D.
Holland, Cory L.
Pertsemlidis, Alexander
Du, Liqin
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
Abstract
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.
Description
Keywords
microRNA-2110, neuroblastoma cell lines, oncosuppressive function, Tsukushi (TSKU), Chemistry and Biochemistry
Citation
Zhao, Z., Partridge, V., Sousares, M., Shelton, S. D., Holland, C. L., Pertsemlidis, A., Du, L. (2018) microRNA-2110 functions as an onco-suppressor in neuroblastoma by directly targeting Tsukushi. PLoS ONE, 13(12) : e0208777.
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Rights Holder
© 2018 Zhao et al.
Rights License
This work is licensed under a Creative Commons Attribution 4.0 International License.