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

摘要

SUMMARY 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.