MiR-20a Induces Cell Radioresistance by Activating the PTEN/PI3K/Akt Signaling Pathway in Hepatocellular Carcinoma
MiR-20a Induces Cell Radioresistance by Activating the PTEN/PI3K/Akt Signaling Pathway in Hepatocellular Carcinoma
复制标题
MiR-20a 通过激活肝细胞癌中的 PTEN/PI3K/Akt 信号通路诱导细胞放射抗性
DOI：
10.1016/j.ijrobp.2015.04.007
复制
发表时间：
2015-08-01
影响因子：
7
通讯作者：
Chen, Longhua
中科院分区：
文献类型：
--
作者：
Zhang, Yuqin;Zheng, Lin;Chen, Longhua
目的：探讨miR-20a在肝细胞癌放射抗性中的作用，为肝癌的治疗提供新的思路。方法：采用实时定量聚合酶链式反应技术检测miR-20a和PTEN在肝癌细胞系及其配对原发灶组织中的表达。用细胞辐射和集落形成实验观察miR-20a对放射增敏的影响。通过生物信息学预测和荧光素酶活性测定鉴定miR-20a的靶标。用磷脂酰肌醇3-激酶抑制剂LY294002抑制Akt的磷酸化，验证miR-20a是否通过激活PTEN/PI3K/Akt通路影响肝癌细胞的放射抗性。结果：miR-20a在肝癌细胞系和组织中表达增加，而PTEN与其呈负相关。MiR-20a在Bel-7402和SMMC-7721细胞中的过表达增强了它们对电离辐射的抗性，而在HCCLM3和QGY-7701细胞中miR-20a的抑制使它们对miR-20a的敏感性增加。PTEN被确定为miR-20a诱导辐射抗性的直接功能靶点。MiR-20a过表达激活了PTEN/PI3K/Akt信号通路。结论：miR-20a通过激活PTEN/PI3K/Akt通路诱导肝癌细胞辐射抵抗，提示miR-20a/PTEN/PI3K/Akt可能成为肝癌有效治疗策略的研究靶点。(C)2015 Elsevier Inc.保留所有权利。
Purpose: To investigate the role of miR-20a in hepatocellular carcinoma (HCC) cell radioresistance, which may reveal potential strategies to improve treatment.Methods and Materials: The expression of miR-20a and PTEN were detected in HCC cell lines and paired primary tissues by quantitative real-time polymerase chain reaction. Cell radiation combined with colony formation assays was administrated to discover the effect of miR-20a on radiosensitivity. Bioinformatics prediction and luciferase assay were used to identify the target of miR-20a. The phosphatidylinositol 3-kinase inhibitor LY294002 was used to inhibit phosphorylation of Akt, to verify whether miR-20a affects HCC cell radioresistance through activating the PTEN/PI3K/Akt pathway.Results: MiR-20a levels were increased in HCC cell lines and tissues, whereas PTEN was inversely correlated with it. Overexpression of miR-20a in Bel-7402 and SMMC-7721 cells enhances their resistance to the effect of ionizing radiation, and the inhibition of miR-20a in HCCLM3 and QGY-7701 cells sensitizes them to it. PTEN was identified as a direct functional target of miR-20a for the induction of radioresistance. Overexpression of miR-20a activated the PTEN/PI3K/Akt signaling pathway. Additionally, the kinase inhibitor LY294002 could reverse the effect of miR-20a-induced radioresistance.Conclusion: MiR-20a induces HCC cell radioresistance by activating the PTEN/PI3K/Akt pathway, which suggests that miR-20a/PTEN/PI3K/Akt might represent a target of investigation for developing effective therapeutic strategies against HCC. (C) 2015 Elsevier Inc. All rights reserved.