Differential Effects of MicroRNAs on Glioblastoma Growth and Migration

• Main Authors: Francesca Peruzzi, Jovanny Zabaleta, Giuseppe Russo, Krzysztof Reiss, Adam Lassak, Marco Pacifici, Duane Jeansonne
• Format: Article
• Language: English
• Published: MDPI AG 2013-03-01
• Series: Genes
• Subjects: Glioblastoma; microRNA; mTOR; CYR61
• Online Access: http://www.mdpi.com/2073-4425/4/1/46

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.