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CNS Neurosci Ther. 2012 Jul;18(7):573-83. doi: 10.1111/j.1755-5949.2012.00344.x. Epub 2012 May 28.

MicroRNA-21 expression is regulated by β-catenin/STAT3 pathway and promotes glioma cell invasion by direct targeting RECK.

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1
Department of Neurosurgery, Tianjin Medical University General Hospital, China.

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.

[Indexed for MEDLINE]

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