Long noncoding RNA RP11-838N2.4 enhances the cytotoxic effects of temozolomide by inhibiting the functions of miR-10a in glioblastoma cell lines.
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, non-resistant 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-β (TGF-β) independent of miR-10a. Finally, Characterization of lncRNA RP11-838N2.4 could contribute to strategies for enhancing the efficacy of TMZ.
The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Yanting
Y
Liu
The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Ningbo
N
Xu
The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Boyang
B
Liu
The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Yiru
Y
Huang
The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Huijun
H
Zeng
The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Zhao
Z
Yang
The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Zhenyan
Z
He
The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Hongbo
H
Guo
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D000077204:Temozolomide; D023041:Xenograft Model Antitumor Assays
D018906:Antineoplastic Agents, Alkylating; C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D003606:Dacarbazine; D000077204:Temozolomide
chemo-resistance; glioblastoma; lncRNA; microarray; temozolomide