M i R ‐21 Modulates h TERT Through a STAT 3‐Dependent Manner on Glioblastoma Cell Growth

摘要

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.