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Knockdown of MCM10 Gene Impairs Glioblastoma Cell Proliferation, Migration and Invasion and the Implications for the Regulation of Tumorigenesis

Abstract

Minichromosome maintenance 10 (MCM10) plays an important role in DNA replication and is expressed in a variety of tumors, including glioma. However, its role and mechanism in glioma remain elusive. The purpose of this study was to examine the molecular function of MCM10 in glioblastoma cell lines in vitro and to further investigate the molecular mechanisms in the network mediated by MCM10. Cell proliferation, invasion, and migration were investigated in the absence of MCM10 mediated by RNA interference (RNAi) in U87 and U251 cell lines. Microarray data were obtained from U87 cells infected with a lentivirus expressing a small interfering RNA (siRNA) targeting MCM10, and ingenuity pathway analysis (IPA) was performed. Molecular signaling pathways, gene functions, and upstream and downstream regulatory genes and networks were analyzed. MCM10 was positively stained in human glioblastoma multiforme (GBM) samples according to immunohistochemistry. Silencing MCM10 in U87 and U251 cells significantly reduced cell proliferation, migration, and invasion. In U87 cells transfected with MCM10, 274 genes were significantly upregulated, while 313 genes were downregulated. IPA revealed that MCM10 is involved in the IGF-1 signaling pathway, and calcitriol appears to be a significant upstream regulator of MCM10. Other factors, such as TWIST1 and Stat3, also interact within the MCM10-mediated network. Our data indicate that MCM10 is involved in the regulation of GBM in vitro and may provide more evidence for understanding the molecular mechanisms of this fatal disease.

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Funding

This work was supported by Beijing Natural Science Foundation (7172041). Peng Kang is supported by Beijing Municipal Administration of Hospitals ‘Youth Program’ (QMS20180512) and Beijing Program of Excellent Young Investigator (2015000021469G221).

Author information

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Peng Kang, Zhe Han, and Heng Zhang. The first draft of the manuscript was written by Peng Kang and Yongji Tian, and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

Correspondence to Wang Jia or Yongji Tian.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Kang, P., Han, Z., Liao, Z. et al. Knockdown of MCM10 Gene Impairs Glioblastoma Cell Proliferation, Migration and Invasion and the Implications for the Regulation of Tumorigenesis. J Mol Neurosci (2020). https://doi.org/10.1007/s12031-020-01486-y

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Keywords

  • MCM10
  • Glioma
  • Proliferation
  • Migration
  • IPA