Abstract:
BACKGROUND:Altered expression of micro(mi)RNAs has been shown to be associated with tumorigenesis and tumor progression. The expression of phosphatase and tensin homolog (PTEN) plays an important role in glioma and is regarded as a prognostic marker of glioma patients. The goal of this study was to investigate the function of lethal (let)-7a miRNA in glioma cell lines with different PTEN phenotypes. METHODS:One hundred ninety-eight glioma tissues were used to profile miRNA expression. RESULTS:Let-7a was shown to have lower expression in high-grade glioma than in low-grade glioma. Low expression of let-7a was correlated with poor prognosis of primary glioblastoma patients. We demonstrated that K-ras was a functional target for let-7a to induce cell cycle arrest, apoptosis, and inhibition of cell migration and invasion in vitro. Our further results showed no difference in malignancy inhibition induced by let-7a in 4 glioma cells, including U87 (PTEN null), U251 (PTEN mutant), LN229 (PTEN wild type), and LN229 (PTEN small interfering RNA). The phosphatidylinositol-3 kinase/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways were inhibited by let-7a, and the inhibition effects had no difference in 4 glioma cells. We demonstrated that let-7a could induce suppression of glioma in vivo by generating a glioma xenograft model. CONCLUSION:Our results indicated that let-7a suppresses its target transcript K-ras and inhibits glioma malignancy independent of PTEN expression.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
Wang XR,Luo H,Li HL,Cao L,Wang XF,Yan W,Wang YY,Zhang JX,Jiang T,Kang CS,Liu N,You YP,Chinese Glioma Cooperative Group (CGCG).doi
10.1093/neuonc/not107subject
Has Abstractpub_date
2013-11-01 00:00:00pages
1491-501issue
11eissn
1522-8517issn
1523-5866pii
not107journal_volume
15pub_type
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