Long noncoding RNA RP11-838N2.4 enhances the cytotoxic effects of temozolomide by inhibiting the functions of miR-10a in glioblastoma cell lines

被引：50

作者：

Liu, Yanting ^{[1
]}

Xu, Ningbo ^{[1
]}

Liu, Boyang ^{[1
]}

Huang, Yiru ^{[1
]}

Zeng, Huijun ^{[1
]}

Yang, Zhao ^{[1
]}

He, Zhenyan ^{[1
]}

Guo, Hongbo ^{[1
]}

机构：

[1] Southern Med Univ, Guangdong Prov Key Lab Brain Funct Repair & Regen, Natl Key Clin Specialty,Engn Technol Res Ctr, Educ Minist China,Dept Neurosurg,Zhujiang Hosp, Guangzhou 510282, Guangdong, Peoples R China

来源：

ONCOTARGET | 2016年 / 7卷 / 28期

基金：

中国国家自然科学基金;

关键词：

lncRNA; glioblastoma; chemo-resistance; temozolomide; microarray; EPITHELIAL-MESENCHYMAL TRANSITION; CANCER STEM-CELLS; TGF-BETA; EXPRESSION PROFILES; MICROARRAY ANALYSIS; THERAPEUTIC TARGET; RESISTANCE FACTORS; GASTRIC-CANCER; APOPTOSIS; GLIOMAS;

D O I：

10.18632/oncotarget.9699

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Resistance to temolozomide (TMZ), the standard chemotherapy agent for treating glioblastomas (GBM), is a major clinical problem for patients with GBM. Recently, long noncoding RNAs (lncRNAs) have been implicated in chemotherapy resistance in various cancers. In this study, we found that the level of the lncRNA RP11-838N2.4 was lower in TMZ-resistant GBM cells (U87TR, U251TR) compared to the parental, nonresistant GBM cells (U87, U251). In GBM patients, the decreased level of lncRNA RP11-838N2.4 correlated with higher risk of GBM relapse, as well as shorter postoperative survival times. We further found that lncRNA RP11-838N2.4 could enhances the cytotoxic effects of temozolomide to GBM cells both in vivo and in vitro. Moreover, lncRNA RP11-838N2.4 acts as an endogenous sponge, suppressing the function of miR-10a through conserved sequences and increasing the expression of EphA8 that enhanced the rate of cell apoptosis, thereby intensified sensitivity of GBM cells to TMZ. Additionally, lncRNA RP11-838N2.4 inhibited the activity of transforming growth factor-beta (TGF-beta) independent of miR-10a. Finally, Characterization of lncRNA RP11-838N2.4 could contribute to strategies for enhancing the efficacy of TMZ.

引用

页码：43835 / 43851

页数：17

共 43 条

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