MiR-124 Acts as a Tumor Suppressor in Glioblastoma via the Inhibition of Signal Transducer and Activator of Transcription 3.

Abstract

MicroRNAs are important regulators of multiple cellular processes, and aberrant miRNA expression has been observed in human glioblastoma (GBM). The present study was to evaluate the level of miR-124 and signal transducer and activator of transcription 3 (STAT3) in GBM tissues and cells. We further investigated the molecular mechanisms of miR-124 and STAT3 in GBM cell lines U87 and U251. Here, we found that miR-124 expression was downregulated in GBM tissues and U87 and U251 cells (all p < 0.001) but not associated with blood routine (RBC, WBC count, etc.) and liver and renal function indicators (all p > 0.05). By contrast, STAT3 was upregulated. Furthermore, the expression of miR-124 was inversely proportional to that of STAT3 mRNA or protein (p = 0.013, p = 0.015, respectively). In vitro studies demonstrated that the overexpression of miR-124 played a suppressor role in the proliferation of U87 and U251 cells and promoted cell apoptosis. Luciferase reporter assays confirmed that miR-124 binding to the 3'-UTR regions of STAT3 inhibited the expression of STAT3 in U87 and U251 cells. However, the inhibitor of miR-124 promoted the expression of STAT3 and cell proliferation. In conclusion, our data suggest that miR-124 may have a potential role in treatment of GBM patients and that miR-124 is a novel regulator of invasiveness and tumorigenicity in GBM cells by targeting STAT3. The miR-124/STAT3 pathway may be a useful therapeutic agent in GBM patients.