MiR-21 modulates hTERT through a STAT3-dependent manner on glioblastoma cell growth.
OBJECTIVE
As an important oncogenic miRNA, miR-21 has been reported to play crucial roles in glioblastoma (GBM) carcinogenesis. However, the precise biological function and molecular mechanism of miR-21 in GBM remain elusive. This study is designed to explore the mechanism of miR-21 involved in the control of GBM cell growth.


RESULTS
MTT assay, cell cycle analysis, and apoptosis analysis showed that reduction of miR-21 inhibited cell growth in U87 and LN229 GBM cells. Further, reduction of miR-21 decreased the expression of human telomerase reverse transcriptase (hTERT) and repressed STAT3 expression and STAT3 phosphorylation. STAT3 inhibition led to a remarkable depletion of hTERT at both mRNA and protein levels by binding to the hTERT gene promoter by performing luciferase reporter assay and chromatin Immunoprecipitation PCR. Finally, knockdown of miR-21 considerably inhibited tumor growth and diminished the expression of STAT3 and hTERT in xenograft model.


CONCLUSIONS
Our findings indicate that miR-21 regulates hTERT expression mediated by STAT3, therefore controlling GBM cell growth.
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, China.
Ying-Yi
YY
Wang
Guan
G
Sun
Hui
H
Luo
Xie-Feng
XF
Wang
Feng-Ming
FM
Lan
Xiao
X
Yue
Lin-Shan
LS
Fu
Pei-Yu
PY
Pu
Chun-Sheng
CS
Kang
Ning
N
Liu
Yong-Ping
YP
You
D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*
C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D019098:Telomerase