Overexpression of minichromosome maintenance protein 10 in medulloblastoma and its clinical implications

Pediatr Blood Cancer. 2017 Dec;64(12). doi: 10.1002/pbc.26670. Epub 2017 Jun 9.

Abstract

Background: Overexpression of minichromosome maintenance (MCM) proteins 2, 3, and 7 is associated with migration and invasion in medulloblastoma (MB). However, expression profiling of all prereplication complex (pre-RC) has not been addressed in MBs.

Procedure: We performed mRNA expression profiling of a large set of pre-RC elements in cell lines and tumor tissues of MB. RNAi technology was employed for functional studies in MB cell lines.

Results: Our data showed that most of the pre-RC components are significantly overexpressed in MB. Among all pre-RC mRNAs, MCM10 showed the highest level of expression (∼500- to 1,000-fold) in MB cell lines and tissues compared to the levels detected in cerebellum. In addition, RNAi silencing of MCM10 caused reduced cell proliferation and cell viability in MB cells.

Conclusions: Taken together, our study reveals that the pre-RC is dysregulated in MB. In addition, MCM10, a member of this complex, is significantly overexpressed in MB and is required for tumor cell proliferation.

Keywords: MCM10; medulloblastoma; minichromosome maintenance protein; prereplication complex.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Cerebellar Neoplasms / chemistry*
  • Cerebellar Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Medulloblastoma / chemistry*
  • Medulloblastoma / pathology
  • Minichromosome Maintenance Proteins / analysis
  • Minichromosome Maintenance Proteins / physiology*

Substances

  • MCM10 protein, human
  • Minichromosome Maintenance Proteins