MiR-20a Induces Cell Radioresistance by Activating the PTEN/PI3K/Akt Signaling Pathway in Hepatocellular Carcinoma

被引：139

作者：

Zhang, Yuqin ^{[1
]}

Zheng, Lin ^{[2
,4
]}

Ding, Yi ^{[1
]}

Li, Qi ^{[3
]}

Wang, Rong ^{[1
]}

Liu, Tongxin ^{[5
]}

Sun, Quanquan ^{[5
]}

Yang, Hua ^{[6
]}

Peng, Shunli ^{[1
]}

Wang, Wei ^{[1
]}

Chen, Longhua ^{[1
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Radiat Oncol, Guangzhou, Guangdong, Peoples R China

[2] Southern Med Univ, Nanfang Hosp, Dept Pathol, Guangzhou, Guangdong, Peoples R China

[3] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangzhou, Guangdong, Peoples R China

[4] Southern Med Univ, Sch Basic Med Sci, Dept Pathol, Guangzhou, Guangdong, Peoples R China

[5] Canc Hosp, Dept Radiat Oncol, Hangzhou, Zhejiang, Peoples R China

[6] Southern Med Univ, Nanhai Hosp, Dept Radiat Oncol, Guangzhou, Guangdong, Peoples R China

来源：

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 2015年 / 92卷 / 05期

关键词：

STEREOTACTIC BODY RADIOTHERAPY; HUMAN CANCER-CELLS; EXPRESSION PROFILES; MICRORNA EXPRESSION; IONIZING-RADIATION; RESISTANCE; CONTRIBUTES; GROWTH; REPAIR;

D O I：

10.1016/j.ijrobp.2015.04.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：1132 / 1140

页数：9

共 32 条

[1]

Radioresistant cervical cancer shows upregulation of the NHEJ proteins DNA-PKcs, Ku70 and Ku86 [J].