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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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.
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(1):46-64.
Jeansonne, Duane; Pacifici, Marco; Lassak, Adam; Reiss, Krzysztof; Russo, Giuseppe; Zabaleta, Jovanny; Peruzzi, Francesca. 2013. "Differential Effects of MicroRNAs on Glioblastoma Growth and Migration." Genes 4, no. 1: 46-64.