Genes 2013, 4(1), 46-64; doi:10.3390/genes4010046
Differential Effects of MicroRNAs on Glioblastoma Growth and Migration
1
LSU Health Sciences Center, Medical School, Stanley S. Scott Cancer Center, 533 Bolivar Street, New Orleans, LA 70112, USA
2
Sbarro Institue for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA
*
Author to whom correspondence should be addressed.
Received: 31 January 2013 / Revised: 15 February 2013 / Accepted: 16 February 2013 / Published: 4 March 2013
(This article belongs to the Special Issue Signal Transduction)
Abstract
Glioblastoma multiforme is characterized by rapid proliferation, aggressive metastatic potential, and resistance to radio- and chemotherapy. The matricellular protein CYR61 regulates cellular proliferation and migration and is highly expressed in Glioblastomas. MicroRNAs are 22-nucleotides long RNAs that regulate gene expression post-transcriptionally. Here, we utilized the LN229 glioblastoma cell line and found that CYR61 is a target of miR-136, miR-155, and miR-634. Over-expression of miR-136 and miR-634 miRNAs negatively affected proliferation, but not migration, while expression of miR-155 reduced migration but did not affect the proliferation of LN229 cells. Investigation of the molecular mechanisms affected by expression of miR-634 revealed an increased phosphorylation of p70S6 kinase, suggesting an induction of the mammalian target of rapamycin (mTOR) complex 1 pathway. Additionally, in miR-634 overexpressing cells, TSC2, a negative regulator of mTOR signaling, was found to be decreased. Altogether, our study provides insights on the differential roles of miRs-136, -155, and -634 in regulating glioblastoma cell growth and migration, and how microRNAs could be manipulated to decrease the aggressiveness and metastatic potential of tumor cells.Keywords:
Glioblastoma; microRNA; mTOR; CYR61
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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MDPI and ACS Style
Jeansonne, D.; Pacifici, M.; Lassak, A.; Reiss, K.; Russo, G.; Zabaleta, J.; Peruzzi, F. Differential Effects of MicroRNAs on Glioblastoma Growth and Migration. Genes 2013, 4, 46-64.