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MicroRNA-29a inhibits glioblastoma stem cells and tumor growth by regulating the PDGF pathway

  • Yanzhi Yang
  • Samantha Dodbele
  • Thomas Park
  • Rainer Glass
  • Krishna Bhat
  • Erik P. Sulman
  • Ying ZhangEmail author
  • Roger AbounaderEmail author
Laboratory Investigation

Abstract

Background and purpose

microRNAs are small noncoding RNAs that play important roles in cancer regulation. In this study, we investigated the expression, functional effects and mechanisms of action of microRNA-29a (miR-29a) in glioblastoma (GBM).

Methods

miR-29a expression levels in GBM cells, stem cells (GSCs) and human tumors as well as normal astrocytes and normal brain were measured by quantitative PCR. miR-29a targets were uncovered by target prediction algorithms, and verified by immunoblotting and 3′ UTR reporter assays. The effects of miR-29a on cell proliferation, death, migration and invasion were assessed with cell counting, Annexin V-PE/7AAD flow cytometry, scratch assay and transwell assay, respectively. Orthotopic xenografts were used to determine the effects of miR-29a on tumor growth.

Results

Mir-29a was downregulated in human GBM specimens, GSCs and GBM cell lines. Exogenous expression of miR-29a inhibited GSC and GBM cell growth and induced apoptosis. miR-29a also inhibited GBM cell migration and invasion. PDGFC and PDGFA were uncovered and validated as direct targets of miR-29a in GBM. miR-29a downregulated PDGFC and PDGFA expressions at the transcriptional and translational levels. PDGFC and PDGFA expressions in GBM tumors, GSCs, and GBM established cell lines were higher than in normal brain and human astrocytes. Mir-29a expression inhibited orthotopic GBM xenograft growth.

Conclusions

miR-29a is a tumor suppressor miRNA in GBM, where it inhibits cancer stem cells and tumor growth by regulating the PDGF pathway.

Keywords

microRNA (miRNA) Glioblastoma (GBM) Glioblastoma stem cells (GSC) Platelet-derived growth factor (PDGF) 

Notes

Acknowledgements

This study was supported by NIH grant UO1 CA CA220841 (Roger Abounader).

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Microbiology, Immunology and Cancer BiologyUniversity of VirginiaCharlottesvilleUSA
  2. 2.Neurosurgical ResearchUniversity Clinics MunichMunichGermany
  3. 3.Department of Translational Molecular PathologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Department of Radiation OncologyNYU Langone School of MedicineNew YorkUSA
  5. 5.Department of NeurologyUniversity of VirginiaCharlottesvilleUSA
  6. 6.Cancer CenterUniversity of VirginiaCharlottesvilleUSA

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