Gliomas are the most common primary tumors of the central nervous system. Rapid proliferation and diffuse brain invasion of these tumors are likely to determine the unfavorable prognosis. Recent studies have shown that ligand activation of peroxisome proliferator-activated receptor γ (PPARγ) can induce differentiation and inhibit proliferation of several cancer cells. In this study, we identified pioglitazone, one PPARγ ligand in particular, suppressed human glioma cells proliferation, migration, and induced glioma cells apoptosis. Concomitantly, expression level of β-catenin protein, a key molecule in carcinogenesis, was decreased in glioma cells treated with pioglitazone. Noteworthy, knockdown of β-catenin expression using siRNA technology mimicked the anti-neoplastic potency of pioglitazone. These results indicate that β-catenin is one of the mediators for pioglitazone to suppress glioma cells growth and invasion. Due to its capacity to counteract β-catenin and glioma cell proliferation and migration, pioglitazone represents a promising drug for adjuvant therapy of glioma and other highly migratory tumor entities.
Previous studies have shown that miR-137 functions as a tumor suppressor in various cancers, but its role in the initiation and development of gliomas is still unknown. Currently, we found that miR-137 exhibited the most significant increase in normal brain tissues compared with glioma specimens, and the miR-137 expression was greatly decreased with the ascending of tumor pathological grades. Furthermore, overexpression of miR-137 in vitro by chemically synthesized miR-137 mimics suppressed the proliferation, inhibited cell cycle arrest in the G1/G0 phase, and induced cell apoptosis. The tumor-suppressive effects of miR-137 were indeed induced by Rac1, which was verified as a direct target of miR-137. These findings indicate that miR-137 inhibits the growth of gliomas cells by directly targeting Rac1, suggesting that miR-137 could be a new important therapeutic strategy for glioma treatment and warrants further investigation.
Aim. To investigate the role and mechanism of miR-15b in the proliferation and apoptosis of glioma. Methods. The miR-15b mimics were transfected into human glioma cells to upregulate the miR-15b expression. Cyclin D1 was determined by both western blotting analysis and luciferase reporter assay. Methylthiazol tetrazolium (MTT) and flow cytometry were employed to detect the cell proliferation, cell cycle, and apoptosis. Results. Overexpression of miR-15b inhibits proliferation by arrested cell cycle progression and induces apoptosis, possibly by directly targeting Cyclin D1. Both luciferase assay and bioinformatics search revealed a putative target site of miR-15b binding to the 3′-UTR of Cyclin D1. Moreover, expression of miR-15b in glioma tissues was found to be inversely correlated with Cyclin D1 expression. Enforced Cyclin D1 could abrogate the miR-15b-mediated cell cycle arrest and apoptosis. Conclusions. Our findings identified that miR-15b may function as a glioma suppressor by targeting the Cyclin D1, which may provide a novel therapeutic strategy for treatment of glioma.
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