MicroRNA-21 Expression is regulated by β-catenin/STAT3 Pathway and Promotes Glioma Cell Invasion by Direct Targeting RECK

Abstract

Aims: MicroRNA-21 (miR-21) expression is increased in many types of human malignancy, including glioma. Recent studies report that miR-21 regulates cell invasion by targeting RECK, however, the underlying transcriptional regulation of miR-21 in glioma cells remains elusive. Results: Here, we identify a positive correlation between miR-21 expression and pathological grade in glioma tissues. We demonstrate that β-catenin pathway regulates miR-21 expression in human umbilical vein endothelial cell and glioma cells, and that this regulation is signal transducer and activator of transcription 3 (STAT3)-dependent. Further, chromatin immunoprecipitation and luciferase reporter analysis demonstrate that miR-21 is controlled by an upstream promoter containing a conserved STAT3 binding site. Notably, knockdown of miR-21-inhibited cell invasion by increasing RECK expression and decreased tumor growth in a xenograft model. Conclusion: These data provide compelling evidence that β-catenin regulation of miR-21 via STAT3 plays a role in glioma cell invasion and proliferation and indicate that STAT3 is a potential therapeutic target for glioma intervention. © 2012 Blackwell Publishing Ltd.