Differential Effects of MicroRNAs on Glioblastoma Growth and Migration

Genes

Duane Jeansonne¹  Marco Pacifici¹  Adam Lassak¹  Krzysztof Reiss¹  Giuseppe Russo²  Jovanny Zabaleta¹ 

[1] LSU Health Sciences Center, Medical School, Stanley S. Scott Cancer Center, 533 Bolivar Street, New Orleans, LA 70112, USA; E-Mails:;Sbarro Institue for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA; E-Mail:

关键词: Glioblastoma;    microRNA;    mTOR;    CYR61;   

DOI  :  10.3390/genes4010046

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.