PTEN公司
癌症研究
基因沉默
骨肉瘤
蛋白激酶B
张力素
PI3K/AKT/mTOR通路
癌基因
基因敲除
生物
癌症
细胞周期
癌变
细胞生长
小RNA
信号转导
细胞凋亡
细胞生物学
基因
生物化学
遗传学
作者
Jie Xiao,Weifeng Yu,Kai‐Ming Hu,Maoqiang Li,Jianwei Chen,Zhanchun Li
出处
期刊:Oncology Reports
[Spandidos Publications]
日期:2017-03-01
卷期号:37 (4): 2513-2521
被引量:34
摘要
MicroRNAs (miRNAs) play critical roles in human cancers including osteosarcoma (OS). miR-92a has been found to be a cancer-related miRNA in many cancer types and it is upregulated in OS cell lines. However, the expression and biological function of miR-92a in OS have not been investigated. In this study, we showed that miR-92a expression was increased in OS tissues, and its high expression was correlated with clinical stage, T classification and histological differentiation. Furthermore, patients with high expression of miR-92a had a significantly poorer survival rate. Functionally, miR-92a overexpression promoted the proliferation and cell cycle progression, and inhibited apoptosis in MG-63 cells. While inhibition of miR-92a showed contrary effects with reduced proliferation, cell cycle arrest at G1 phase and increased apoptosis in U2OS cells. Moreover, we confirmed that miR-92a inhibition reversed the tumor growth of OS cells in nude mice. Phosphatase and tensin homolog (PTEN), a well-known tumor suppressor, was confirmed to be the direct downstream target of miR-92a in OS. Notably, miR-92a consequently regulated the expression of the downstream targets of PTEN/AKT signaling pathway including p-Akt(Ser473), mTOR, p-p27(Thr157) and p-MDM2(Ser166). Furthermore, PTEN knockdown abrogated the functional effects of miR-92a silencing on the proliferation, apoptosis and cell cycle progression in OS cells. Thus, miR-92a that exerts an oncogenic role by targeting PTEN/AKT pathway in OS potentially acts as a biomarker and drug-target.
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