Open AccessM i R ‐21 Modulates h TERT Through a STAT 3‐Dependent Manner on Glioblastoma Cell Growth
Author(s) -
Wang YingYi,
Sun Guan,
Luo Hui,
Wang XieFeng,
Lan FengMing,
Yue Xiao,
Fu LinShan,
Pu PeiYu,
Kang ChunSheng,
Liu Ning,
You YongPing
Publication year - 2012
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/j.1755-5949.2012.00349.x
Subject(s) - telomerase reverse transcriptase , cell growth , chromatin immunoprecipitation , chemistry , telomerase , stat3 , gene knockdown , microbiology and biotechnology , cancer research , signal transduction , biology , apoptosis , gene expression , gene , promoter , biochemistry
Summary Background and purpose As an important oncogenic mi RNA , mi R ‐21 has been reported to play crucial roles in glioblastoma ( GBM ) carcinogenesis. However, the precise biological function and molecular mechanism of mi R ‐21 in GBM remain elusive. This study is designed to explore the mechanism of mi R ‐21 involved in the control of GBM cell growth. Methods and results MTT assay, cell cycle analysis, and apoptosis analysis showed that reduction of mi R ‐21 inhibited cell growth in U 87 and LN 229 GBM cells. Further, reduction of mi R ‐21 decreased the expression of human telomerase reverse transcriptase (h TERT ) and repressed STAT 3 expression and STAT 3 phosphorylation. STAT 3 inhibition led to a remarkable depletion of h TERT at both m RNA and protein levels by binding to the h TERT gene promoter by performing luciferase reporter assay and chromatin Immunoprecipitation PCR . Finally, knockdown of mi R ‐21 considerably inhibited tumor growth and diminished the expression of STAT 3 and h TERT in xenograft model. Conclusion Our findings indicate that mi R ‐21 regulates h TERT expression mediated by STAT 3, therefore controlling GBM cell growth.