MiRNA expression profiling in migrating Glioblastoma cells: Regulation of cell migration and invasion by miR-23b via targeting of Pyk2

Joseph C Loftus, Julianna T D Ross, Kimberly M. Paquette, Vincent M. Paulino, Sara Nasser, Zhongbo Yang, Jean Kloss, Seungchan Kim, Michael E. Berens, Nhan Tran

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Background: Glioblastoma (GB) is the most common and lethal type of primary brain tumor. Clinical outcome remains poor and is essentially palliative due to the highly invasive nature of the disease. A more thorough understanding of the molecular mechanisms that drive glioma invasion is required to limit dispersion of malignant glioma cells. Methodology/Principal Findings: We investigated the potential role of differential expression of microRNAs (miRNA) in glioma invasion by comparing the matched large-scale, genome-wide miRNA expression profiles of migrating and migration-restricted human glioma cells. Migratory and migration-restricted cell populations from seven glioma cell lines were isolated and profiled for miRNA expression. Statistical analyses revealed a set of miRNAs common to all seven glioma cell lines that were significantly down regulated in the migrating cell population relative to cells in the migration-restricted population. Among the down-regulated miRNAs, miR-23b has been reported to target potential drivers of cell migration and invasion in other cell types. Over-expression of miR-23b significantly inhibited glioma cell migration and invasion. A bioinformatics search revealed a conserved target site within the 3′ untranslated region (UTR) of Pyk2, a non-receptor tyrosine kinase previously implicated in the regulation of glioma cell migration and invasion. Increased expression of miR-23b reduced the protein expression level of Pyk2 in glioma cells but did not significantly alter the protein expression level of the related focal adhesion kinase FAK. Expression of Pyk2 via a transcript variant missing the 3′UTR in miR-23b-expressing cells partially rescued cell migration, whereas expression of Pyk2 via a transcript containing an intact 3′UTR failed to rescue cell migration. Conclusions/Significance: Reduced expression of miR-23b enhances glioma cell migration in vitro and invasion ex vivo via modulation of Pyk2 protein expression. The data suggest that specific miRNAs may regulate glioma migration and invasion to influence the progression of this disease.

Original languageEnglish (US)
Article numbere39818
JournalPLoS One
Volume7
Issue number6
DOIs
StatePublished - Jun 22 2012

Fingerprint

cell invasion
Glioblastoma
MicroRNAs
cell movement
Glioma
Cell Movement
Cells
microRNA
cells
protein synthesis
non-specific protein-tyrosine kinase
Focal Adhesion Protein-Tyrosine Kinases
cell lines
Proteins
3' Untranslated Regions
Bioinformatics
Protein-Tyrosine Kinases
3' untranslated regions
Tumors
lethal genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

MiRNA expression profiling in migrating Glioblastoma cells : Regulation of cell migration and invasion by miR-23b via targeting of Pyk2. / Loftus, Joseph C; Ross, Julianna T D; Paquette, Kimberly M.; Paulino, Vincent M.; Nasser, Sara; Yang, Zhongbo; Kloss, Jean; Kim, Seungchan; Berens, Michael E.; Tran, Nhan.

In: PLoS One, Vol. 7, No. 6, e39818, 22.06.2012.

Research output: Contribution to journalArticle

Loftus, Joseph C ; Ross, Julianna T D ; Paquette, Kimberly M. ; Paulino, Vincent M. ; Nasser, Sara ; Yang, Zhongbo ; Kloss, Jean ; Kim, Seungchan ; Berens, Michael E. ; Tran, Nhan. / MiRNA expression profiling in migrating Glioblastoma cells : Regulation of cell migration and invasion by miR-23b via targeting of Pyk2. In: PLoS One. 2012 ; Vol. 7, No. 6.
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AU - Paulino, Vincent M.

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AB - Background: Glioblastoma (GB) is the most common and lethal type of primary brain tumor. Clinical outcome remains poor and is essentially palliative due to the highly invasive nature of the disease. A more thorough understanding of the molecular mechanisms that drive glioma invasion is required to limit dispersion of malignant glioma cells. Methodology/Principal Findings: We investigated the potential role of differential expression of microRNAs (miRNA) in glioma invasion by comparing the matched large-scale, genome-wide miRNA expression profiles of migrating and migration-restricted human glioma cells. Migratory and migration-restricted cell populations from seven glioma cell lines were isolated and profiled for miRNA expression. Statistical analyses revealed a set of miRNAs common to all seven glioma cell lines that were significantly down regulated in the migrating cell population relative to cells in the migration-restricted population. Among the down-regulated miRNAs, miR-23b has been reported to target potential drivers of cell migration and invasion in other cell types. Over-expression of miR-23b significantly inhibited glioma cell migration and invasion. A bioinformatics search revealed a conserved target site within the 3′ untranslated region (UTR) of Pyk2, a non-receptor tyrosine kinase previously implicated in the regulation of glioma cell migration and invasion. Increased expression of miR-23b reduced the protein expression level of Pyk2 in glioma cells but did not significantly alter the protein expression level of the related focal adhesion kinase FAK. Expression of Pyk2 via a transcript variant missing the 3′UTR in miR-23b-expressing cells partially rescued cell migration, whereas expression of Pyk2 via a transcript containing an intact 3′UTR failed to rescue cell migration. Conclusions/Significance: Reduced expression of miR-23b enhances glioma cell migration in vitro and invasion ex vivo via modulation of Pyk2 protein expression. The data suggest that specific miRNAs may regulate glioma migration and invasion to influence the progression of this disease.

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