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• Jeansonne, D
• Pacifici, M
• Lassak, A
• Reiss, K
• Russo, G
• Zabaleta, J
• Peruzzi, F
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• Jeansonne, D
• Pacifici, M
• Lassak, A
• Reiss, K
• Russo, G
• Zabaleta, J
• Peruzzi, F
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• Jeansonne, D
• Pacifici, M
• Lassak, A
• Reiss, K
• Russo, G
• Zabaleta, J
• Peruzzi, F

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Genes 2013, 4(1), 46-64; doi:10.3390/genes4010046

Article

Differential Effects of MicroRNAs on Glioblastoma Growth and Migration

Duane Jeansonne ¹, Marco Pacifici ¹, Adam Lassak ¹, Krzysztof Reiss ¹, Giuseppe Russo ², Jovanny Zabaleta ¹ and Francesca Peruzzi ^1,*

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; in revised form: 15 February 2013 / Accepted: 16 February 2013 / Published: 4 March 2013

(This article belongs to the Special Issue Signal Transduction)

Download PDF Full-Text [347 KB, uploaded 4 March 2013 08:28 CET]

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

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