Overexpressed let-7a inhibits glioma cell malignancy by directly targeting K-ras, independently of PTEN
Overexpressed let-7a inhibits glioma cell malignancy by directly targeting K-ras, independently of PTEN
复制标题
过表达的 let-7a 通过直接靶向 K-ras 来抑制神经胶质瘤细胞恶性肿瘤，而与 PTEN 无关。
DOI：
10.1093/neuonc/not107
复制
发表时间：
2013-11-01
期刊：
影响因子：
15.9
通讯作者：
You, Yong-Ping
中科院分区：
文献类型：
--
作者：
Wang, Xi-Rui;Luo, Hui;You, Yong-Ping
背景
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.