Differential Effects of MicroRNAs on Glioblastoma Growth and Migration.
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.
LSU Health Sciences Center, Medical School, Stanley S. Scott Cancer Center, 533 Bolivar Street, New Orleans, LA 70112, USA. djean1@lsuhsc.edu.
Duane
D
Jeansonne
LSU Health Sciences Center, Medical School, Stanley S. Scott Cancer Center, 533 Bolivar Street, New Orleans, LA 70112, USA. mpacif@lsuhsc.edu.
Marco
M
Pacifici
LSU Health Sciences Center, Medical School, Stanley S. Scott Cancer Center, 533 Bolivar Street, New Orleans, LA 70112, USA. alassa@lsuhsc.edu.
Adam
A
Lassak
LSU Health Sciences Center, Medical School, Stanley S. Scott Cancer Center, 533 Bolivar Street, New Orleans, LA 70112, USA. kreiss@lsuhsc.edu.
Krzysztof
K
Reiss
Sbarro Institue for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA. grusso@temple.edu.
Giuseppe
G
Russo
LSU Health Sciences Center, Medical School, Stanley S. Scott Cancer Center, 533 Bolivar Street, New Orleans, LA 70112, USA. jzabal@lsuhsc.edu.
Jovanny
J
Zabaleta
LSU Health Sciences Center, Medical School, Stanley S. Scott Cancer Center, 533 Bolivar Street, New Orleans, LA 70112, USA. fperuz@lsuhsc.edu.
Francesca
F
Peruzzi