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


CONCLUSIONS
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.
Department of Neurosurgery, Tianjin Medical University General Hospital, China.
Lei
L
Han
Xiao
X
Yue
Xuan
X
Zhou
Feng-Ming
FM
Lan
Gan
G
You
Wei
W
Zhang
Kai-Liang
KL
Zhang
Chun-Zhi
CZ
Zhang
Jin-Quan
JQ
Cheng
Shi-Zhu
SZ
Yu
Pei-Yu
PY
Pu
Tao
T
Jiang
Chun-Sheng
CS
Kang
D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques / Q000379:methods; D018390:Gene Targeting / Q000379:methods; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D051176:beta Catenin / Q000502:physiology*
C495270:CTNNB1 protein, human; D058851:GPI-Linked Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C115460:RECK protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051176:beta Catenin