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.
AIMS: MicroRNA-21 (miR-21) expression is increased in many types of humanmalignancy, 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.
Authors: Kenji Zennami; Su Mi Choi; Ross Liao; Ying Li; Wikum Dinalankara; Luigi Marchionni; Fatema H Rafiqi; Akira Kurozumi; Koji Hatano; Shawn E Lupold Journal: Mol Cancer Res Date: 2018-12-05 Impact factor: 5.852
Authors: Jalahalli M Siddesha; Anthony J Valente; Tadashi Yoshida; Siva S V P Sakamuri; Patrice Delafontaine; Hideo Iba; Makoto Noda; Bysani Chandrasekar Journal: Cell Signal Date: 2014-01-19 Impact factor: 4.315