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XRN2 Is Required for Cell Motility and Invasion in Glioblastomas.

Abstract
One of the major obstacles in treating brain cancers, particularly glioblastoma multiforme, is the occurrence of secondary tumor lesions that arise in areas of the brain and are inoperable while obtaining resistance to current therapeutic agents. Thus, gaining a better understanding of the cellular factors that regulate glioblastoma multiforme cellular movement is imperative. In our study, we demonstrate that the 5'-3' exoribonuclease XRN2 is important to the invasive nature of glioblastoma. A loss of XRN2 decreases cellular speed, displacement, and movement through a matrix of established glioblastoma multiforme cell lines. Additionally, a loss of XRN2 abolishes tumor formation in orthotopic mouse xenograft implanted with G55 glioblastoma multiforme cells. One reason for these observations is that loss of XRN2 disrupts the expression profile of several cellular factors that are important for tumor invasion in glioblastoma multiforme cells. Importantly, XRN2 mRNA and protein levels are elevated in glioblastoma multiforme patient samples. Elevation in XRN2 mRNA also correlates with poor overall patient survival. These data demonstrate that XRN2 is an important cellular factor regulating one of the major obstacles in treating glioblastomas and is a potential molecular target that can greatly enhance patient survival.
AuthorsTuyen T Dang, Megan Lerner, Debra Saunders, Nataliya Smith, Rafal Gulej, Michelle Zalles, Rheal A Towner, Julio C Morales
JournalCells (Cells) Vol. 11 Issue 9 (04 28 2022) ISSN: 2073-4409 [Electronic] Switzerland
PMID35563787 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
Chemical References
  • RNA, Messenger
  • Exoribonucleases
  • XRN2 protein, human
Topics
  • Animals
  • Brain Neoplasms (metabolism)
  • Cell Movement (genetics)
  • Cell Proliferation
  • Exoribonucleases (metabolism)
  • Glioblastoma (metabolism)
  • Humans
  • Mice
  • Neoplastic Processes
  • RNA, Messenger (therapeutic use)

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